1 s2.0 S2405844024081726 Main

Heliyon 10 (2024) e32141
Contents lists available at ScienceDirect
Heliyon
journal homepage: www.cell.com/heliyon
Research article
Assessment of Helicobacter pylori cytotoxin-associated Gene A (Cag

A) protein and its association with ferritin and vitamin B12
deficiencies among adult healthy asymptomatic residents in
Sharjah, United Arab Emirates
Om Kolthoom M. Weisy a, Reena A. Kedia b, Ibrahim Mahmoud c,
Raed O. Abu Odeh b, d, Bashair M. Mussa e, Salah Abusnana f, g, Sameh S.M. Soliman h,
Jibran Sualeh Muhammad b, e, Mohamad Hamad b, d, Rose Ghemrawi i, j,
Ghalia Khoder a, b, *
a
Department of Pharmaceutics and Pharmaceuticals Technology, College of Pharmacy, University of Sharjah, Sharjah, United Arab Emirates
b
Research Institute for Medical & Health Sciences, University of Sharjah, United Arab Emirates
c
Department of Family and Community Medicine and Behavioral Sciences, College of Medicine, University of Sharjah, Sharjah, United Arab
Emirates
d
Department of Medical Laboratory Sciences, College of Health Sciences, University of Sharjah, Sharjah, United Arab Emirates
e
Department of Basic Medical Sciences, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates
f
Diabetes and Endocrinology Department, University Hospital Sharjah, Sharjah, United Arab Emirates
g
Clinical Science Department, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates
h
Department of Medicinal Chemistry, College of Pharmacy, University of Sharjah, Sharjah, United Arab Emirates
i
College of Pharmacy, Al Ain University, Abu Dhabi, United Arab Emirates
j
AAU Health and Biomedical Research Center, Al Ain University, Abu Dhabi, United Arab Emirates
A R T I C L E I N F O A B S T R A C T
Keywords: Introduction: The United Arab Emirates (UAE) serves as an effective epidemiological site for
H. pylori assessing Helicobacter pylori (H. pylori) infection due to its diverse population. However,
CagA comprehensive studies on the prevalence of H. pylori in the UAE are notably scarce. In depth
Vitamin B12
prevalence studies are needed as a preventive measure against gastric cancer and other emerging
Ferritin
ELISA
extra gastric diseases associated with H. pylori infection. Aim: This study aimed to assess H. pylori
Gastric cancer infection and its virulent oncoprotein, the Cytotoxin-Associated Gene (Cag A) and its association
Sharjah with ferritin and vitamin B12 deficiencies. Methods: The study was conducted on 1094 healthy
UAE asymptomatic volunteers residents in the Sharjah Emirate, UAE. Enzyme-linked immunosorbent
assay (ELISA) was performed to assess H. pylori infection using H. pylori antibodies (IgG), and
detection of CagA protein using Cag A antibody (IgG) in the human serum. Ferritin and vitamin
B12 serum levels were assessed and correlated to H. pylori infection. Results: This study focuses
mainly on the assessment of H. pylori and its virulent factor CagA, in relation to vitamin B12 and
ferritin deficiencies. Remarkably, 49.6 % of the participants were detected positive for H. pylori,
with over half of these cases involving CagA positive strains. Notably, among Emirati participants,
76.11 % of those with H. pylori infection were CagA positive. Statistical analysis revealed a
* Corresponding author. Department of Pharmaceutics and Pharmaceuticals Technology, College of Pharmacy, University of Sharjah, Sharjah,
United Arab Emirates.
E-mail address: [email protected] (G. Khoder).
https://doi.org/10.1016/j.heliyon.2024.e32141
Received 4 January 2024; Received in revised form 28 May 2024; Accepted 29 May 2024
Available online 29 May 2024
2405-8440/© 2024 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license
(http://creativecommons.org/licenses/by/4.0/).
O.K.M. Weisy et al. Heliyon 10 (2024) e32141
significant correlation between H. pylori, CagA level, and ferritin/vitamin B12 deficiencies.
Conclusion: These findings emphasize the importance of timely detection and eradication of
H. pylori not only as a preventive strategy against gastric cancer but also as an effective strategy to
rescue the adverse effects from ferritin and vitamin B12 deficiencies, thereby improving the
overall health outcomes of individuals affected by H. pylori infection.
1. Introduction
Helicobacter pylori (H. pylori) is a microaerophilic, Gram-negative bacillus that infects approximately half of the population,
exhibiting significant geographic variability in prevalence [1–4]. H. pylori is primarily transmitted through oral-oral or fecal-oral
routes within families, especially in environments with poor sanitation and hygiene practices [3,5]. The prevalence of H. pylori is
usually high in developing countries (85–95 %) compared to developed countries (30–50 %) [2,3,6]. Despite advancements in
sanitation and eradication methods, the epidemiology of H. pylori infection continues to exhibit a significant increase. This prevalence
remains particularly high in developing countries, where it is influenced by socioeconomic status and hygiene levels. Currently, 4.4
billion people worldwide are estimated to be have H. pylori infection [2].
H. pylori infection is typically acquired during childhood and often remains asymptomatic. It can persist throughout life if not
treated with antibiotics and progress to various gastric diseases including chronic and acute gastritis, peptic and duodenal ulcers,
gastric cancer (GC) and mucosa-associated lymphoid tissue (MALT) lymphoma [7,8]. Furthermore, several controversial studies have
also demonstrated a link between H. pylori and iron-deficiency anemia, ferritin deficiency, vitamin B12 deficiency, and certain cases of
idiopathic thrombocytopenic purpura [9–16].
Among gastric and extra gastric diseases associated to H. pylori, GC remains the most serious disease attributed to this bacterium.
Despite declining incidence rates, the global burden of GC is projected to increase by 62 % by 2040 [17]. In the Arab region, including
the United Arab Emirates (UAE), the estimated age-standardized incidence rates showed an incidence rate of 4.4 per 100 000 pop
ulations [18]. Several experimental and meta-analysis studies have attributed the gastric carcinogenesis of H. pylori to the
cytotoxin-associated antigen A (CagA), one of the key virulence genes in H. pylori [19–26]. The translocation of the oncoprotein CagA
into gastric epithelial cells, facilitated by the Type IV Secretion System (T4SS), is associated with GC [19]. Due to this potent interactive
mechanism, the World Health Organization (WHO) has classified H. pylori as a class 1 carcinogen and one of the strongest risk factors
for GC and MALT lymphoma [27].
H. pylori strains are commonly categorized as either CagA-positive or CagA-negative. The presence of CagA is frequently associated
with mucosal inflammation and severe gastrointestinal conditions, such as peptic ulcers and GC [28]. Notably, approximately 30–40 %
of Western H. pylori strains are CagA-negative, in contrast to nearly all East Asian H. pylori isolates, which are CagA-positive [29,30].
The incidence of GC is closely linked to the global prevalence of H. pylori [31,32]. Screening and eradication of H. pylori are
cost-effective strategies that can significantly reduce the burden of GC in high-prevalence populations, offering potential to decrease
GC-related mortality [33–36].
In the latest global prevalence study conducted in 2018, data on the prevalence of H. pylori in the United Arab Emirates (UAE) were
conspicuously missing among the 62 countries examined. The absence of informative data on H. pylori in the UAE, highlights the need
to accurately assess the prevalence of H. pylori infection in UAE. Addressing this knowledge gap would be invaluable in understanding
the epidemiological landscape of H. pylori in the UAE and provide appropriate preventive and management strategies.
Since H. pylori is well known by its genetic diversity and geographic variability, UAE constitutes a relevant site to conduct related
epidemiological studies due to the multi nationalities and ethnicities residing in the country. Over the past three decades, 34 studies
concerning H. pylori infection in the UAE have been conducted, according to PubMed data. However, only a limited number of these
studies have assessed the H. pylori in asymptomatic subjects [37–39]. A recent pilot study conducted in 2019 found that 41 % of the
UAE population was infected with H. pylori. The study identified a significant association between H. pylori infection and several
sociodemographic factors and gastrointestinal characteristics of the participants [39]. Despite the intriguing nature of the findings and
their novelty, it is crucial to acknowledge that the study was limited by its small sample size, consisting of only 350 participants.
Furthermore, the investigation failed to assess key virulence factors, notably the oncoprotein CagA, as well as important clinical
parameters such as ferritin and vitamin B12 levels, which are suggested as clinical outcomes of H. pylori infection. Growing evidence
suggests a potential association between H. pylori infection, ferritin and vitamin B12 deficiencies [40–49].
Since implementation of effective eradication strategies necessitates accurate and updated information regarding the local prev
alence of H. pylori, the current study was conducted. Due to the significant global differences in the prevalence of H. pylori infection and
GC, it is crucial for each country to evaluate the necessity of implementing a national screening and treatment program for H. pylori. In
the case of UAE, comprehensive evaluation is warranted to determine the cost-effectiveness of such a program before its nationwide
implementation. Up to date, there is no enough comprehensive national studies assessing H. pylori and its associated factors. Hence, the
primary aims of this study are to assess H. pylori infection and its oncoprotein CagA on a large screen population representative of the
different ethnicities residing in the UAE including the Emirati nationals. The secondary aim is to investigate the association between
H. pylori, CagA seropositivity, ferritin and vitamin B12 deficiencies.
2
2. Materials and methods
Ethical Statement
The study received review and approval from the Research and Ethics Committee of the University of Sharjah under reference
number REC-17-04-17-01. The study involved the collection of sociodemographic data from healthy volunteer participants, which was
recorded and handled with utmost confidentiality. Prior to participating in the study, all volunteers provided their informed consent by
signing a consent form. These measures were taken to ensure that the study adhered to ethical guidelines and protected the privacy of
the participants.
2.1. Study design, sample size and sample preparation
The cross-sectional study was conducted from January 2022 to January 2023. During this period, 1094 serum samples were
sequentially collected from healthy asymptomatic volunteers at the Sharjah Municipality Public Health Clinic (SMPHC).
The sample size was determined using an online sample size calculator (https://www.calculator.net/sample-size-calculator.html).
The calculation used a 95 % confidence level, 3 % margin of error, 40 % estimated prevalence from a previous study, and a population
of 11 million [50]. Initially, 1025 participants were suggested, but 1094 were included to account for potential data exclusions.
The study included participants from both sexes with a mean age of 40.1 years (±14.59). Serum samples were collected using serum
separator tubes (SST). The samples were permitted to clot for 2 h at room temperature or overnight at 4 ◦ C, followed by centrifugation
at 1000×g for 15 min. Approximately 1000 μL of serum were collected and were transported without delay to Research Institute for
Medical & Health Sciences (RIMHS) laboratory, University of Sharjah, where aliquots of fresh serum samples were stored at − 20 ◦ C or
− 80 ◦ C for further screening. Socio-demographic data (gender, age, nationality, and occupation) were obtained in parallel with the
Table 1
Socio-demographic profiles of the study participants according to
gender, age, ethnicity, occupation, H. pylori infection and CagA
status, vitamin B12 status (pmol/L) and ferritin status (ng/ml), n
= 1094.
Variable n (%)/Mean (SD)
Gender
Female 715 (65.4)
Male 379 (34.6)
Age, years
Mean (SD) 40.10 (14.59)
19–29 297 (27.1)
30–39 334 (30.5)
40–49 213 (19.5)
50–59 117 (10.7)
≥60 133 (12.2)
Ethnicity
Arab 275 (25.1)
Asian 766 (70.0)
African 44 (4.1)
Western 9 (0.8)
Occupation
Professional 221 (20.2)
Laborer 416 (38)
Food industry 102 (9.3)
Housewife/maid wife 172 (15.7)
Student 36 (3.3)
Unemployed 147 (13.5)
Hp infection status
Negative 551 (50.4)
Positive 543 (49.6)
Vitamin B12 status, pmol/L
Mean (SD) 350 (326.8)
Normal 706 (64.6)
Deficient 388 (35.4)
Ferritin status, ng/ml
Mean (SD) 202.8 (220)
Normal 1026 (93.8)
Deficient 68 (6.2)
CagA status
Negative 776 (70.9)
Positive 318 (29.1)
SD= Standard Deviation.
3
collected serum samples. The purpose of the study was explained briefly to study participants prior to sample collection by the
recruited research assistant. Serum samples were processed for further steps only after a signed consent from by the study participants.
To ensure the study was accessible and comprehensible to participants of all nationalities, the consent form was prepared in both
Arabic and English. Participants from 38 nationalities were involved in the study. For analysis purpose, participants were grouped into
four main ethnicities residents in UAE as follows: Asian (N = 766, 70 %); Arab (N = 275, 25.1 %); African (N = 444.1 %) and Western
(N = 9, 0.8 %). Arabs were mainly from the following countries: UAE, Jordan, Iraq, Syria, Egypt, and Palestine. Asians were mainly
from Pakistan, India, Bangladesh, Nepal, Philippine, and Indonesia. Africans were mainly from Sudan, and Ethiopia. A summary of the
detailed socio-demographic profiles of the study participants is provided in Table 1.
For the exclusion and inclusion criteria of this study, participants were disqualified if they 1) experienced recent gastrointestinal
disturbances, 2) had undergone any antimicrobial treatments within the past two weeks, or 3) had received H. pylori treatment within
the last six months. These criteria ensured that the study focused on predominantly healthy, asymptomatic individuals to accurately
assess the prevalence of H. pylori. Participants who were receiving treatments for ferritin or vitamin B12 deficiencies were also
excluded. The study population comprised healthy expatriate residents of various nationalities and occupations, as well as Emirati
participants aged 19 years and older, residing in the UAE.
2.2. PREMIER H. pylori serum test
The PREMIER H. pylori (Ref: 606096, Meridian BIOSCIENCE, USA) is an enzyme immunoassay (EIA) designed for the qualitative
detection of IgG antibodies to H. pylori in human serum in vitro. This assay uses a sonicated H. pylori bacterial cell lysate that is coated
onto plastic microwells. Patient serum samples were diluted and incubated in these wells at temperatures between 19 ◦ C and 27 ◦ C.
Following the incubation, the wells were washed to remove unbound substances, and then a peroxidase-conjugated monoclonal
antibody specific to human IgG was added. The plates were subsequently reincubated to allow for binding. After a second washing step
to eliminate any unbound antibody conjugate, PREMIER Substrate I was introduced to the wells to facilitate color development, which
occurs in response to the presence of the enzyme-linked antibody. To halt the reaction and stabilize the color, PREMIER Stop Solution I
was added. The reactions were observed either visually or spectrophotometrically by reading the absorbance at 450 nm within 10 min
of adding PREMIER Stop Solution I. Visual reading yields a negative result when the sample appears colorless and a positive result
when the sample shows a definite yellow color. Spectrophotometric measurements at a single wavelength of 450 nm were interpreted
as negative if the optical density (OD450) is less than 0.12 and positive if it is equal to or greater than 0.12. For optimal performance,
all samples and controls were assayed in duplicate.
2.3. CagA ELISA test
The Human cytotoxin-associated protein (CagA) antibody (IgG) ELISA kit (Cat. # CSB-EQ027541HU; Cusabio, Houston, TX, USA)
was utilized to quantify the IgG levels against the CagA protein in serum. This assay employed a pre-coated antigen microtiter plate to
measure the expression levels. The ELISA kit includes a microtiter plate pre-coated with an antigen specific to CagA antibody. Samples
containing potential antibodies are added to the wells. Anti-human IgG conjugated with Horseradish Peroxidase (HRP) is also added,
which will bind to any antibodies specific to the pre-coated antigen. After incubation, the wells are washed to remove any unbound
reagents, ensuring that only the antibodies bound to the pre-coated antigen remain in the wells. A substrate solution is introduced,
which reacts with the HRP enzyme linked to the bound antibodies, producing a color change. The intensity of this color is directly
proportional to the amount of antibody bound to the antigen in the wells. The reaction is stopped by adding a stopping solution, and
the color intensity is measured. This intensity correlates with the concentration of the human cytotoxin-associated protein antibody in
the sample. Samples and all reagents were prepared as previously described [51].
A negative result is obtained when the optical density (OD) value of the sample well is less than 2.1 times the OD value of the
negative control. In contrast, a positive result is obtained when the OD value of the sample well is equal to or greater than 2.1 times the
OD value of the negative control. For optimal performance, same samples and controls were assayed in duplicate. All samples stored at
− 20 ◦ C or − 80 ◦ C were tested within 1 month and 2 months, respectively to avoid loss of bioactivity and contamination. The assay
present high sensitivity and specificity for detecting CagA antibody and does not present any significant cross-reactivity or interference
between CagA and analogues.
2.4. Vitamin B12 ELISA test
Vitamin B12 ELISA kit (REF: EIA- 5848, DRG International, USA) was used to measure the concentration of serum vitamin B12.
Essential reagents such as an antibody, enzyme-antigen conjugate, and native antigen are used. Initially, a biotinylated antibody is
mixed with a serum that contains the antigen, prompting a binding reaction. Following a brief incubation period, an enzyme conjugate
is introduced, leading to a competitive reaction with the antigen for a limited number of antibody binding sites. Concurrently, the
biotin on the antibody reacts with the streptavidin on the microwell, which facilitates the separation of the antibody-bound fraction
through decantation or aspiration. The level of enzyme activity in this fraction is inversely related to the concentration of the native
antigen. By comparing this activity against a dose-response curve created using serum references with known antigen concentrations,
the antigen level in an unknown sample can be accurately determined. All samples and reagents were prepared following the man
ufacturer’s protocol. Absorbance was read at 450 nm within 15 min of adding the stop solution. Samples suspected of concentrations
higher than 2000 pg/mL were diluted to 1:5 and 1:10 with Vitamin B12 calibrator and re-assayed. Based on the manufacturer reference
4
values, a serum vitamin B12 concentration below 148 pmol/L in adults below or equal to 60 years old, was considered as vitamin B12
deficiency condition. While a serum level below 81 pmol/L in adults above 60 years was considered as a vitamin B12 deficient
condition. For optimal performance, all samples and controls were assayed in duplicate.
2.5. Ferritin ELISA test
The Ferritin ELISA kit (REF: EIA-4408, DRG International, USA) operates on the principle of simultaneous binding of human ferritin
to two monoclonal antibodies—one immobilized on microwell plates and the other conjugated with horseradish peroxidase (HRP).
Samples and reagents were prepared in accordance with the manufacturer’s instructions. Following incubation, bound/free separation
was achieved through a straightforward solid-phase washing. Subsequently, the TMB substrate was added. After allowing sufficient
time for color development, the enzyme reaction was halted, and absorbance was measured. Ferritin concentration in the sample was
calculated using a series of standards, with color intensity being directly proportional to ferritin concentration. Absorbance values for
the standards were plotted against their respective concentrations, and the mean absorbance value for each sample was determined
based on this standard curve. The concentrations of the samples in ng/mL were obtained by interpolating their absorbance values on
the standard curve. Based on the manufacturer reference values, a range of [6–180 ng/ml] and [8–350 ng/ml] were considered as a
normal ranges of serum ferritin in premenopausal and post-menopausal women, respectively. A range of [20–400 ng/ml] was
considered as a normal level of serum ferritin in men. An obtained concentration less than 6 ng/ml in women or 20 ng/ml in men was
reported as a ferritin deficiency condition. For optimal performance, all samples and controls were assayed in duplicate.
2.6. Statistical analysis
Descriptive statistics were used to summarize the characteristics of the study participants. Continuous variables were reported as
means with standard deviations (SD), while categorical variables were presented as frequencies and percentages. Pearson’s chi-square
test examined the relationship between H. pylori infection and categorical variables such as gender, age groups, ethnicity, occupation,
vitamin B12 status, ferritin status, and CagA status. To identify factors associated with H. pylori infection, binary logistic regression
analysis was conducted. A p-value of ≤0.05 was considered statistically significant. All analyses were performed using IBM SPSS
Statistics for Windows, version 28.0 (IBM Corp., New York, USA).
Table 2
Bivariate analysis of H. pylori infection in relation to socio-demographic profiles, vitamin B12, and ferritin deficiencies among study participants
(n = 1094).
Variables Hp infection status, n (%) P value
Negative, n = 551 Positive, n = 543
Gender
Female 212 (55.9) 167 (44.1) 0.007
Male 339 (47.4) 376 (52.6)
Age, years
19–29 137 (36.1) 160 (53.9)
30–39 170 (50.9) 164 (49.1)
40–49 113 (53.1) 100 (46.9) 0.286
50–59 56 (47.9) 61 (52.1)
≥60 75 (56.4) 58 (43.6)
Ethnicity
Arab 148 (53.8) 127 (46.2)
Asian 382 (49.9) 384 (50.1)
African 13 (29.5) 31 (70.5) 0.002
Western 8 (89.9) 1 (11.1)
Occupation
Professional 118 (53.4) 103 (46.6)
Laborer 181 (43.5) 235 (56.5)
Food industry 56 (54.9) 46 (45.1) 0.011
Housewife/maid wife 93 (54.1) 79 (45.9)
Student 24 (66.7) 12 (33.3)
Unemployed 79 (53.7) 68 (46.3)
Normal 364 (51.6) 342 (48.4) 0.394
Deficient 187 (48.2) 201 (51.8)
Normal 540 (52.6) 486 (47.3) < 0.001
Deficient 11 (16.2) 57 (83.8)
The P value was determined using Pearson’s chi-square test. Statistically significant P values are highlighted in bold.
5
3. Results
3.1. Socio-demographic profile of study participants
A total of 1094 volunteer subjects were included in the current epidemiological study (Table 1). Among participants, there were
715 (65.4 %) females and 379 (34.6 %) males. The participants’ ages ranged from 19 to 70 years, with an average age of 40.10 ± 14.59
years. Among the studied age groups, participants aged between 19 and 39 years constituted the largest group (631, 57.6 %). While,
the age group from 50 to 59 years constituted the fewest number of participants (117, 10.7 %). The ethnicity of the participants was
distributed as follows: Arab (275, 25.1 %), Asian (766, 70.0 %), African (44, 4 %), and Western (9, 0.8 %). The ethnicity of the
participants was distributed over 38 nationalities residents in UAE, The major nationalities of the participants were distributed as
following: Indian (363, 33.2 %), Pakistani (175, 16 %), Emiratis (147, 13.4 %), Bangladeshi (101, 9.2 %), Filipino (58, 5.3 %),
Egyptian (48, 4.4 %), Syrian (40, 3.7 %), Nepali (33, 3 %), Ethiopian (18, 1.64 %) and Sudanese (13, 1.2 %). While remaining minor
nationalities represented around 8.96 % of the total participants. Only very few participants from the Western ethnicity participated in
this study maybe because the emirate of Sharjah is usually hosted by more Arab and Asians residents compared to the other emirates.
In terms of occupation, it was distributed as following: employed as laborer (417, 38 %), employed as professional (221, 20.2 %),
employed as maid wife and housewife (172, 15.7 %), employed as worker in food industry (102, 9.3 %), and student (36, 3.3 %). Non
employed participants constituted 13.5 % (Table 1).
3.2. Assessment of H. pylori infection, CagA, vitamin B12 and ferritin
Analysis of the 1094 collected serum samples revealed that 543 individuals were infected with H. pylori, resulting in an estimated
infection rate of 49.6 % (Table 1). Interestingly, among the total participants (n = 1094), 318 (29.1 %) were found infected with a
CagA positive strain which accounts to 58.5 % from the total number of H. pylori positive participants (n = 543). Regarding the serum
vitamin B12, 706 (64.6 %) of the participants showed a normal vitamin B12 levels, while 388 (35.4 %) showed vitamin B12 deficiency.
The mean value of the vitamin B12 status of all participants was 350 ± 326.8 pmol/L. Similarly, most of the participants showed
normal serum ferritin level (1026, 93.8 %) compared to only 68 participants (6.2 %) with ferritin deficiency. The mean value of the
ferritin status of all participants was 202.8 ± 220 ng/ml.
3.3. Correlation of H. pylori infection with socio-demographic profiles, vitamin B12, and ferritin deficiencies
Bivariate analysis revealed significant differences in H. pylori infection based on gender, ethnicity, occupation, and ferritin defi
ciency (Table 2). Males were more prone to infection (376, 52.6 %) compared to females (167, 44.1 %), with a significant statistical
difference (p = 0.007). No significant difference was found between H. pylori infection and age groups. The age groups from 19 to 29
and 50 to 59 presented the highest percentages of infection (53.9 % and 52.1 %, respectively).
Given the diverse ethnic composition of the UAE, it was important to examine which ethnic groups are more susceptible to H. pylori
infection. The analysis revealed significant statistical difference in H. pylori infection rates among the different ethnicities (p = 0.002)
(Table 2). The African ethnicity presented the highest H. pylori prevalence (31, 70.5 %) while Arab ethnicity presented the lower
prevalence (127, 46.2 %). The Asian ethnicity presented a very close prevalence to Arab ethnicity (384, 50.1 %) and was ranked two
among the tested ethnicities. Due to the small number of western participants, the obtained results were mostly neglected (Fig. 1).
In terms of nationality, the Ethiopian, Sudanese, and Bangladeshi participants presented the highest percentage of H. pylori
infection (83 %, 69.2 %, 68.3 % respectively). The lowest H. pylori prevalence was obtained among Filipino participants (27.6 %).
Almost half (45.57 %) of the Emiratis subjects were found infected by H. pylori (Fig. 2). Therefore, the UAE nationals ranked among the
second top highest in H. pylori prevalence among the tested Arab ethnicity.
A statistically significant difference was observed between H. pylori infection and participants’ occupations, including pro
fessionals, laborers, food industry workers, housewives, students, and the unemployed (p = 0.011). Laborers exhibited the highest
infection rate (235, 56.5 %), followed by professional workers (103, 46.6 %), housewives and maids (79, 45.9 %), food industry
workers (46, 45.1 %), and students (12, 33.3 %) (Table 2).
Regarding vitamin B12 deficiency, 201 participants with H. pylori infection were found to be deficient in vitamin B12. Thus, the
Fig. 1. H. pylori infection (%) across the different study participants ethnicities.
6
Fig. 2. H. pylori infection (%) across the main study participants nationalities.
prevalence of vitamin B12 deficiency among H. pylori-positive participants was determined to be 51.8 %. Although 35.4 % of the study
participants had vitamin B12 deficiency, and previous research has linked this deficiency to H. pylori infection, no statistically sig
nificant association was found between H. pylori infection and vitamin B12 deficiency among UAE residents. However, a significant
difference was observed between H. pylori infection and ferritin deficiency (p < 0.001). Of the 68 participants with ferritin deficiency
(6.2 % of the total study population), 57 (83.8 %) tested positive for H. pylori (Table 2).
Conversely, binary logistic regression analysis indicated that male participants are significantly more likely to be diagnosed with
H. pylori infection compared to female participants (Odds Ratio (OR) 1.74, 95 % CI, 1.22–2.49, p = 0.002). Additionally, individuals of
African descent were found to be more susceptible to the infection (OR 3.45, 95 % CI, 1.55–7.71, p = 0.002) compared to Arab and
Asian ethnicities. In terms of occupation, laborers were more susceptible to the infection (Odds Ratio (OR) 1.41, 95 % CI, 1.01–1.99, p
= 0.05) compared to professionals, food industry workers, housewives and maids, students, and the unemployed (Table 3). Inter
estingly, the ferritin deficiency was also found as risk factor for H. pylori infection on the tested population. Participants with ferritin
deficiency were significantly more susceptible to H. pylori infection (OR 3.69, 95 % CI 2.39–5.69, p < 0.001) compared to those with
normal ferritin levels.
3.4. Correlation between CagA positivity and socio-demographic profiles, vitamin B12 and ferritin deficiencies
Bivariate analysis showed that the oncoprotein CagA exhibited statistically significant differences across several sociodemographic
characteristics including gender, age, and ethnicity, vitamin B12 and ferritin levels (Table 4). Female participants were more likely to
be CagA seropositive (121, 72.5 %) compared to male participants (197, 52.4 %), with this difference being statistically significant (p
< 0.001). Unlike H. pylori status, CagA status showed a statistically significant difference across different age groups (p < 0.001). CagA
Table 3
Binary logistic regression analysis for factors associated with H. pylori infection, n = 1094.
Variable OR (95%CI) P value
Gender
Female Reference
Male 1.74 (1.22–2.49) 0.002
Ethnicity
Arab Reference
Asian 0.89 (0.59–1.35) 0.586
African 3.45 (1.55–7.71) 0.002
Western 0.40 (0.08–1.96) 0.257
Occupation
Professional Reference
Laborer 1.41 (1.01–1.99) 0.050
Food industry 0.87 (0.54–1.41) 0.573
Housewife/maid wife 1.12 (0.69–1.84) 0.644
Student 0.56 (0.25–1.24) 0.150
Unemployed 1.13 (0.65–1.94) 0.668
Normal Reference < 0.001
Deficient 3.69 (2.39–5.69)
CI stands for Confidence Interval; P values were calculated using the binary logistic regression
model. Statistically significant P values are highlighted in bold.
7
Table 4
Factors associated with CagA seropositivity among H. pylori infected patients, n = 543.
Variable Cag A status, n (%) P value
Negative, n = 225 Positive, n = 318
Gender
Female 46 (27.5) 121 (72.5) < 0.001
Male 179 (47.6) 197 (52.4)
Age, years
19–29 91 (56.9) 69 (43.1)
30–39 71 (43.3) 93 (56.7)
40–49 35 (35.0) 65 (65.0) < 0.001
50–59 14 (23.0) 47 (77.0)
≥60 14 (24.1) 44 (75.9)
Ethnicity
Arab 39 (30.7) 88 (69.3) < 0.001
Asian 182 (47.4) 202 (52.6)
African 4 (12.9) 27 (87.1)
Normal 192 (56.1) 150 (43.9) < 0.001
Deficient 33 (16.4) 168 (83.6)
Normal 209 (43) 277 (57) 0.013
Deficient 16 (28) 41 (72)
The P value was determined using Pearson’s chi-square test. Statistically significant P values are highlighted in bold.
seropositivity was found to increase significantly with age. Participants aged 50 years presented the highest prevalence in CagA (>75
%). Additionally, a statistically significant difference was observed between CagA seropositivity and ethnicity (p < 0.001). African
ethnicity presented the highest prevalence with CagA H. pylori strain (87.1 %) followed by Arab and Asian ethnicities (69.3 % and 52.6
%, respectively). Among all the included nationalities, it’s interesting to mention that similarly to the H. pylori status, Ethiopians
presented the highest prevalence with CagA (72.2 %). Even though, Indian, Pakistani, and Bangladeshi presented a high H. pylori
prevalence, this was not reflected at the CagA level where they presented the lowest prevalence in CagA (27 %, 29 %, 26.7 % and 29.16
%, respectively). However, among the Emirati participants, its worthy to mention that among the 45.57 % H. pylori positive partic
ipants, 76.11 % were found infected with CagA positive H. pylori strain and therefore ranked as second after the Syrian Arab par
ticipants (Fig. 3). The other nationalities were neglected due to the small representative sample size.
In contrast to H. pylori status, no significant statistical association was found between CagA seropositivity and participants’ oc
cupations (Table 4). However, a statistically significant difference was observed between the oncoprotein CagA and both vitamin B12
deficiency (p < 0.001) and ferritin deficiency (p = 0.013) (Table 4). Among the 201 H. pylori-infected participants with vitamin B12
deficiency, 168 (83.6 %) were infected with the CagA-positive H. pylori strain, while 33 (16.4 %) were infected with the CagA-negative
strain (Fig. 4). Fig. 4 illustrates the association between vitamin B12 deficiency and seropositivity for H. pylori and its virulence factor,
CagA, in 1094 study participants. It highlights that 35.4 % (388 participants) had vitamin B12 deficiency, of whom 51.8 % (201
participants) tested positive for H. pylori. Among these H. pylori positive individuals, 83.6 % (168 participants) were also CagA positive.
The figure notes a statistically significant correlation between CagA seropositivity and vitamin B12 deficiency (p < 0.001).
Similarly, among the 57 ferritin deficient H. pylori infected participants, 41 (72 %) were infected with the carcinogenic strain of
H. pylori compared to 16 (28 %) who were infected with a noncarcinogenic H. pylori strain (Fig. 5). Fig. 5 illustrates the relationship
Fig. 3. CagA seropositivity (%) among the different study participants nationalities.
8
Fig. 4. Association of vitamin B12 deficiency with H. pylori and CagA seropositivity.
Fig. 5. Association of ferritin deficiency with H. pylori and CagA seropositivity.
between ferritin deficiency and seropositivity for H. pylori and CagA among 1094 participants. It shows that 6.2 % (68 participants)
had ferritin deficiency, of which 83.8 % (57 participants) tested positive for H. pylori. Among these H. pylori positive participants, 72 %
(41 participants) were also CagA positive. The associations between ferritin deficiency and both H. pylori infection and CagA sero
positivity were statistically significant, with p-values of less than 0.001 and 0.013, respectively.
4. Discussion
Epidemiological studies play an essential role in the implementation of eradication and preventive strategies within the overall
management of H. pylori, including identification of specific risk factors and prevention of GC. Based on the latest estimates released by
GLOBOCAN, in 2020, GC is classified as the fourth leading cause of cancer-related mortality [52]. It was reported in over one million
new cases in 2020 alone and was the cause of approximately 769 000 deaths [52]. In the Arab region, including the UAE, the estimated
incidence rates showed an incidence rate of 4.4 per 100 000 populations [18]. Around 90 % of GC cases are linked to H. pylori infection
[50]. In 2018, 812 000 cases were reported, making up about 37 % of all cancers caused by chronic infections, highlighting H. pylori as
the leading carcinogenic pathogen [53]. The lifetime risk of developing GC in those infected with H. pylori ranges from 1 % to 5 %,
influenced by ethnicity and environmental factors [33,54,55]. Several studies have attributed the gastric carcinogenesis of this bac
teria to the cytotoxin associated antigen A (CagA), one of the key virulence genes in H. pylori [20–25]. The oncoprotein CagA protein is
first injected into gastric epithelial cells via T4SS. Following its translocation into the host gastric cell, CagA plays an important role in
the development of local neoplasia [56–60]. Additionally, reports have indicated associations between H. pylori infection and diseases
affecting organs beyond the stomach [8,61]. Growing evidence suggests a potential association between H. pylori infection, ferritin and
vitamin B12 deficiencies [40–47]. However, it is important to note that the evidence supporting these connections is limited,
inconsistent, and inconclusive. While only few observational studies have demonstrated a correlation between the oncoprotein CagA
and the vitamin B12 deficiency [43], none of the clinical studies have investigated the association between the CagA oncoprotein and
the ferritin deficiency. Based on the strong implication of H. pylori and its oncoprotein CagA in GC as well as in other extra-gastric
diseases, it become crucial to eradicate this bacterial infection as a preventive measure toward GC especially in countries where
the prevalence of both GC and H. pylori is high. To this purpose, the 2015 Kyoto H. pylori conference and the 2019 Taipei consensus
strongly endorses the eradication of H. pylori in asymptomatic patients as a preventive measure from GC [33,35,36]. Furthermore, the
consensus proposes that populations with an elevated risk of GC contemplate the implementation of widespread screening initiatives
9
coupled with H. pylori eradication efforts [1]. It is now widely accepted that the incidence rates of GC are closely linked to the global
prevalence of H. pylori infection [31,32]. Research indicates that screening and eradicating H. pylori is a relatively cost-effective
strategy for lowering the incidence of GC and peptic ulcers, particularly in populations with high infection rates. This approach
shows significant potential for reducing mortality related to GC. In a recent study, Chen et al. assessed H. pylori infection among
asymptomatic individuals in China. Their findings indicated that this approach was both more cost-effective and more efficient than
not screening, in terms of preventing GC, peptic ulcers, and non-ulcer dyspepsia [62]. Therefore, to effectively implement eradication
strategies, it is essential to have current data on the local prevalence of H. pylori and its related factors. Given the significant global
variation in the prevalence of H. pylori infection and GC, each country should assess the need for a national H. pylori screening and
treatment program.
Taking together the emerging evidence of association between H. pylori and its oncoprotein CagA and Ferritin and Vitamin B12
deficiency and the lacking studies related to ferritin and vitamin B12 in UAE, this prompted us to conduct this present study.
The success of epidemiological study relies in priority on the sample size and the employed diagnostic tool. In our study, we have
included 1094 participants from the major four ethnicities resident in the UAE. This is the first large H. pylori assessment study
conducted in UAE. The suggested sample size was initially 1025 participants; however, in our study, we included 1094 participants to
account for any equivocal data that may have been removed during the study. Regarding diagnostic tests, each method for detecting
H. pylori serves different purposes and has its own limitations [63,64]. The gold standard for H. pylori detection is endoscopic ex
amination combined with gastric biopsy culture, which is known for its high reliability. However, this approach is expensive and
logistically challenging for epidemiological studies because it requires specialized medical facilities and equipment [5,65]. Molecular
techniques like PCR offer the advantage of testing antimicrobial susceptibility but still rely on the availability of gastric biopsy.
Considering the limitations of previous tests, serological tests remain the most suitable and widely used tool for epidemiological
screening [66,67]. Unlike other diagnostic tests, serological tests are cheap, simple, rapid and do not require an endoscopic exami
nation or bacterial culture [68]. Furthermore, they are reliable and robust enough to be extensively used in several clinical epide
miological studies [1,69–72]. Our study selected the PREMIER H. pylori serology test largely because it does not require invasive
procedures. The PREMIER H. pylori test is designed for the in vitro qualitative detection of IgG antibodies to H. pylori in human serum.
Although serological tests require a phlebotomist and are not as accurate as some other tests, they have been widely and successfully
used in epidemiological studies [63,64]. One of the major advantages of serological testing is that they can detect past and active
H. pylori infections [73]. Even though, detection of past infection could be a disadvantage of the test when used for eradication
confirmation, in our current research study, it was an advantage because our aim was to assess asymptomatic participants with both
current infection and past infection. Unlike other stool tests, the PREMIER H. pylori serum test is the only test not influenced by the
current Proton Pump Inhibitor (PPI) intake [1,69–71]. It is also noteworthy that numerous studies have demonstrated that serological
tests, when compared to the gold standard urea breath test (UBT) for H. pylori detection, yield reliable and comparable results [72].
Furthermore, serological tests seem ideal for epidemiological studies because they may provide additional data on the virulence of the
H. pylori by detecting antibodies against CagA antigen [74]. To this purpose, the human CagA immunoglobulin G (IgG) ELISA test has
been also selected to assess the CagA seropositivity among participants. In detecting H. pylori by ELISA, it is generally recommended to
use two different antibody types for increased specificity and accuracy. The most used immunoglobulins are the IgG and IgM anti
bodies in the ELISA test. IgG antibodies provide high sensitivity and are suitable for detecting both current and past H. pylori infections.
In our study, we have only used one of the immunoglobulin IgG to detect H. pylori and CagA due to the large sample size, the duplicated
samples, and the restricted budget for this study. This is one of the limitations to be considered in further epidemiological studies.
Additionally, the study’s geographic scope was confined to Sharjah due to challenges in obtaining multi-regional ethical approvals,
limiting the diversity of the population sample. We recognize that extending the study to include other emirates would enhance the
generalizability of our findings across the diverse ethnic landscape of the UAE.
The current study was conducted to address the limited availability of data concerning H. pylori, its oncogenic virulence factors
CagA, and associated risk factors, with the aim of contributing new insights to this field of research. Previous investigations conducted
in the UAE have reported varying prevalence rates of H. pylori infection, with outcomes influenced by the specific focus of each study.
Adeyemi et al., in 1992 and Zaitoun et al., in 1994 observed a prevalence of 90 % among dyspeptic patients [75,76]. A study conducted
by Albawardi et al., in 2013, investigating complications of sleeve gastrectomies has found H. pylori infection in 44 % of patients [77].
In 2007, Bener et al. explored the link between type 2 diabetes mellitus and H. pylori infection, discovering a prevalence of 76.7 %
among diabetic subjects, compared to 64.8 % in non-diabetic subjects [78]. Earlier, Bener et al. conducted two studies in 2002 and
2006 that examined the seroprevalence of H. pylori in asymptomatic Emirati patients [37,38]. The initial prospective study, which
included 151 subjects from both farming and non-farming backgrounds, reported H. pylori prevalence rates of 74.2 % using IgG an
tibodies and 51 % using IgA antibodies, with no significant difference in prevalence between farmers and non-farmers [38]. Addi
tionally, a study focusing on asymptomatic individuals from low socioeconomic backgrounds revealed H. pylori prevalence rates of
78.4 % in industrial workers compared to 64.3 % in control workers, showing a statistically significant difference between the two
groups [37]. More recently, a 2019 study reported a prevalence rate of 41 % among a restricted population of 350 participants,
including both children and adults. This study identified significant associations between H. pylori infection, some socio-demographic,
and gastrointestinal characteristics of the patients [39]. However, the study’s scope was limited to a specific population and did not
assess H. pylori virulence factors and other risk factors such as ferritin and vitamin B12 deficiency. Even though previous referenced
studies have contributed to the understanding of H. pylori prevalence in the UAE and have reflected the diversity of prevalence rates
across different study populations and contexts, they were not representative of the UAE population. They primarily focused on
dyspeptic individuals or specific occupational groups [37,38]. In summary, none of these studies considered the asymptomatic
multinational residents in the UAE neither the H. pylori carcinogenic virulent factor CagA, and their association with vitamin B12 and
10
ferritin deficiencies. In our study, approximately half of the healthy volunteered subjects (49.6 %) were found H. pylori positive while
58.5 % were CagA positive. Our findings were comparable to Arab neighboring country such as Oman (49.1 %) but lower than Saudi
Arabia [2], Bahrain [79], Kuwait [80], Jordan and Iraq [81,82]. Compared to African countries such as Egypt and Ethiopia, our results
have showed also lower prevalence [6,83–86]. Compared to Asian countries such as India and Bangladesh, H. pylori prevalence in
adults was estimated to 90 % and 88 %, respectively. The high prevalence of H. pylori in Asian countries was not reflected on the Asian
ethnicity residing in the UAE. However, it was mainly reflected on the African ethnicity. In summary, despite the multi-nationalities
and the multi-ethnicities of the UAE residents, the prevalence of H. pylori remains low compared to Arab, Asian and African countries
and aligned with the declining global prevalence of H. pylori from 55 % to 43 % during the 2014–2020 [2,32].
In the current study, the prevalence of H. pylori and its oncoprotein CagA was assessed in asymptomatic healthy adults residing in
UAE. Additionally, we examined the associations between H. pylori infection and socio-demographic characteristics such as age,
gender, ethnicity, occupation, as well as clinical parameters like ferritin and vitamin B12 deficiencies. The findings of the current study
will provide a valuable and strong foundation for future implementation of national program related to the prevention of GC associated
to H. pylori infection as well as to urge the necessity to conduct future H. pylori antibiotic resistance prevalence studies.
Our findings indicated a significant difference in H. pylori and CagA positivity between genders. Male participants exhibited a
higher prevalence of H. pylori infection (p = 0.007), whereas female participants were more frequently infected with CagA-positive
strains (p < 0.001). The gender disparity in H. pylori infection requires further research to understand how sex affects the acquisi
tion and persistence of the infection. Further investigations are required to explore whether estrogen hormone could affect the
infectivity with the oncoprotein CagA. Regarding age, our findings indicated no significant correlation between the prevalence of
H. pylori infection and different adult age groups. However, there was a statistically significant difference in CagA positivity among age
groups (p < 0.001), particularly in individuals over 50 years old. These results align with findings from other studies [87]. In terms of
ethnicity susceptibility to H. pylori infection and CagA seropositivity, the African ethnicity was most prone to the infection and
particularly to the CagA strains. These findings align with a previous cohort study indicating that Black and African Americans are
more susceptible to GC compared to other ethnic groups in the US. This increased risk is attributed to lower rates of H. pylori testing and
eradication, leading to a higher likelihood of chronic infection [88].
Furthermore, Brown et al., has reported through a systematic review that among five studies investigating H. pylori CagA preva
lence based on race, four reported a higher H. pylori prevalence among Blacks and Hispanics in comparison to whites. In these studies,
the prevalence of CagA varied widely, ranging from 19 % to 77 % among whites, 62 %–90 % among Blacks, and 64 %–74 % among
Hispanics [89,90]. In the Arab ethnicity, Emirati participants presented one of the highest prevalence of H. pylori (45.57 %). This could
be explained by the close interaction between the Emiratis population and Indians through their lifestyle. It is very popular in the UAE
to recruit cooks from India because Indian food is one of the most popular cuisines among local dishes. Furthermore, around 76.11 % of
the Emiratis H. pylori positive participants were infected by the CagA positive strain. Further investigations might be needed in the
future to confirm these results within a restricted Emiratis participants including children and adults. Among the African ethnicity,
Ethiopians represented the highest prevalence to both H. pylori and CagA. These findings were previously reported by Khoder et al., in
2019 where Ethiopian babysitters also presented the highest H. pylori infection in a cross-sectional fecoprevalence study conducted on
350 participants.
In terms of ferritin and vitamin B12 deficiencies, our study found a significant association between H. pylori and ferritin deficiency
only. However, the virulent oncoprotein CagA was found significantly correlated to both vitamin B12 and ferritin deficiencies. Several
literature reviews have shown controversial studies related to H. pylori, ferritin and vitamin B12 deficiencies [40–42,44–48,91–94]
while few studies have explored the correlation between the oncoprotein CagA and ferritin, vitamin B12 deficiencies [43,95]. In the
current study, the association between H. pylori, CagA, ferritin and vitamin B12 in the UAE population was investigated for the first
time on a large scale. In UAE, studies assessing the prevalence of vitamin B12 deficiency are scarce. Only one recent study has revealed
significant alterations of the vitamin B12 serum levels on a restricted population of one-year laparoscopic sleeve gastrectomy (LSG)
patients. Vitamin B12 deficiency was assessed in 28 % of the patients compared to normal (5 %) (p < 0.001) [96]. Similarly, very few
studies have assessed the ferritin deficiency in the UAE population. A study conducted in 2013 in UAE involving 394 participants
revealed noteworthy findings. Among the women included in the study, it was observed that 16 % had iron deficiency anemia while 65
% of the women exhibited low ferritin values, with levels below 30 μg/L [97]. In our study, the prevalence of vitamin B12 and ferritin
deficiencies was assessed to 35.4 % and 6.2 %, respectively. Even though this was not the main objective of our study, these findings
were obtained for the first time and further studies need to be conducted to assess the deficiencies of those serum biomarkers into more
oriented studies due to their implications in various health conditions.
Ferritin, a key protein involved in iron storage and homeostasis, has gained significant attention in clinical research due to its
diverse implications in various health conditions. Alterations in ferritin levels have been associated with a wide range of conditions,
including iron deficiency anemia, chronic inflammation, and certain chronic diseases [98,99]. Emerging evidences and several studies
have suggested potential link between H. pylori and ferritin levels through multiple mechanisms. Firstly, H. pylori-associated chronic
inflammation can lead to impaired iron absorption in the stomach, resulting in reduced iron availability for the synthesis of ferritin.
Secondly, H. pylori-induced gastritis may disrupt the normal functioning of gastric parietal cells, which are involved in the release of
gastric acid and intrinsic factor necessary for efficient iron absorption [46,100]. Consequently, impaired iron absorption can
contribute to reduced ferritin levels [101–104]. Furthermore, H. pylori infection has been associated with an increased risk of
developing iron deficiency anemia, further emphasizing the potential association between H. pylori, and altered ferritin status [46].
However, it is important to note that the relationship between H. pylori and ferritin is complex and influenced by various factors such as
individual host characteristics, coexisting conditions, and the specific H. pylori strain. It has been found that the presence of CagA
positive H. pylori strains may influence ferritin levels in infected individuals. CagA has been shown to interact with cellular signaling
11
pathways and disrupt normal cellular processes, including iron metabolism. Experimental studies have demonstrated that CagA can
interfere with iron uptake and storage mechanisms in host cells, leading to alterations in ferritin levels [12]. Furthermore, CagA has
been found to promote chronic inflammation and oxidative stress, both of which can affect iron homeostasis and contribute to changes
in ferritin levels. In our study, statistically significant association has been found between H. pylori, CagA and ferritin deficiency. The
specific mechanisms through which CagA influences ferritin regulation are still being investigated, but it is believed that CagA may
play a role in the disruption of cellular iron metabolism. However, further research is needed to fully understand the complex interplay
between H. pylori, CagA and ferritin and its implications in H. pylori-related diseases and iron-related disorders. Understanding the
association between ferritin and H. pylori infection may contribute to improved management approaches for individuals affected by
H. pylori-related gastrointestinal disorder.
On the other hand, H. pylori has been proposed to interfere with the absorption of vitamin B12, also known as cobalamin, which is
an essential micronutrient with diverse roles in numerous physiological processes. Its clinical significance lies in its vital functions,
including red blood cell production, nervous system maintenance, and DNA synthesis [105]. Deficiency of vitamin B12 can lead to
various health complications, such as megaloblastic anemia, neuropathy, and cognitive impairment [105]. The malabsorption of the
vitamin B12 induced by H. pylori seems to be related to an impaired production of the intrinsic factor [106] which is produced by
gastric parietal cells to bind to vitamin B12, allowing its absorption in the terminal part of the small intestine [107].
H. pylori-associated gastritis can disrupt the normal functioning of these parietal cells, leading to a decreased intrinsic factor pro
duction. Consequently, individuals infected with H. pylori may experience impaired absorption of vitamin B12, resulting in lower
levels of this essential vitamin. Therefore, it is crucial to consider the potential effects of H. pylori infection on vitamin B12 levels and to
monitor individuals with H. pylori-related gastritis for vitamin B12 deficiency, ensuring accurate diagnosis and appropriate treatment.
In our study, no statistical difference was observed between H. pylori and vitamin B12. However, a significant association was
particularly found between the oncoprotein CagA and vitamin B12. Our findings are in agreement with several studies which have
reported no correlation between H. pylori and vitamin B12 [42,108,109]. Rassol et al., reported no impact of H. pylori on the vitamin
B12 level, folate and homocysteine levels [42]. Likewise, H. pylori infection was not recognized as a risk factor for low vitamin B12
levels in alcohol-dependent patients or in rural Mexican women [108,109]. However, it was reported by Abu Hilu et al., that H. pylori
was negatively correlated to serum levels of vitamin B12 and may contribute to this deficiency [94]. Furthermore, there is a growing
evidence suggesting a potential link between CagA protein of H. pylori and vitamin B12 levels [43,110]. Our results were aligned with
similar study conducted on Turkish population where vitamin B12 deficiency was positively correlated with CagA positivity [43].
However, it’s important to note that the link between CagA and Vitamin B12 levels is complex and influenced by other factors, such as
the host’s genetic predisposition and the presence of other coexisting conditions. Further research is needed to better understand the
underlying mechanisms and clinical implications of the interaction between CagA and vitamin B12 in H. pylori infection.
The study offers a detailed overview of the prevalence of H. pylori and the oncoprotein CagA in the Sharjah Emirate, UAE. It takes
into account the four major ethnicities, the multinational resident population, and various sociodemographic factors associated with
the infection. Furthermore, the assessment of H. pylori and its virulent oncoprotein CagA and their association with ferritin and vitamin
B12 deficiencies have been investigated for the first time. These data can strengthen national efforts aimed at preventing and erad
icating H. pylori, ultimately reducing the complications and outcomes associated with the infection, such as GC. Understanding the link
between H. pylori infection, CagA, and deficiencies in ferritin and vitamin B12 may enhance management strategies for individuals
with H. pylori-related gastrointestinal disorders. Additional large-scale and multicenter epidemiological studies are being planned
across the seven Emirates of the UAE to further this research.
5. Conclusions
Epidemiological studies conducted on H. pylori have underscored its pivotal role in evidence-based decision-making for the
development and implementation of comprehensive management strategies. This is especially crucial in reducing the considerable
burden of H. pylori infection and its associated adverse outcomes, notably GC. Effective eradication strategies demand current,
location-specific data on H. pylori prevalence and its contributing factors. For the first time in the Sharjah Emirate, UAE, this study
assessed the prevalence of H. pylori, the presence of its carcinogenic virulent factor CagA, and their associated risk factors including
vitamin B12 and ferritin deficiencies among 1094 healthy asymptomatic adults. Strikingly, nearly half of the study participants tested
positive for H. pylori, with over half of these cases involving the more virulent CagA positive strains. Notably, among Emirati par
ticipants, 76.11 % of those with H. pylori infection were CagA positive. Statistical analysis demonstrated a significant association
between H. pylori infection and CagA status with gender, ethnicity, occupation, as well as deficiencies in ferritin and vitamin B12.
These findings underscore the importance to prompt H. pylori detection and eradication, not only as a preventive measure against GC
but also as an effective strategy to mitigate adverse effects on ferritin and vitamin B12 deficiencies, thereby enhancing overall health
outcomes for individuals affected by H. pylori infection. The insights from this study will contribute to the establishment of accurate
prevalence estimates of H. pylori and inform the development of efficient future national interventions and strategies.
Funding
This research was funded by targeted research grant (1801110229) and competitive research grant (2201110266) at University of
Sharjah.
12
Ethics declaration
The study received review and approval from the Research and Ethics Committee of the University of Sharjah under reference
number REC-17-04-17-01. All participants provided informed consent to participate in the study.
Data availability Statement
Data associated with the study has not been deposited into a publicly available repository. Data will be made available on request.
CRediT authorship contribution statement
Om Kolthoom M. Weisy: Writing – review & editing, Investigation, Formal analysis. Reena A. Kedia: Methodology, Investigation,
Formal analysis. Ibrahim Mahmoud: Writing – review & editing, Validation, Formal analysis. Raed O. Abu Odeh: Writing – review &
editing, Resources. Bashair M. Mussa: Writing – review & editing, Resources, Methodology. Salah Abusnana: Writing – review &
editing, Resources, Methodology. Sameh S.M. Soliman: Writing – review & editing, Methodology, Funding acquisition. Jibran
Sualeh Muhammad: Writing – review & editing, Validation, Investigation. Mohamad Hamad: Writing – review & editing, Inves
tigation. Rose Ghemrawi: Writing – review & editing, Resources, Methodology. Ghalia Khoder: Writing – review & editing, Writing –
original draft, Resources, Project administration, Methodology, Funding acquisition, Formal analysis, Conceptualization.
Declaration of competing interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to
influence the work reported in this paper.
Acknowledgments
We express our sincere gratitude to the University of Sharjah for their financial and technical support of this research. We also
extend our appreciation to all the volunteer participants involved in this study. Special thanks are due to Mr. Abdelmunim Dafalla of
the Sharjah Municipality Public Health Clinic and to the laboratory staff for their continuous support and for providing the data and
samples essential for this work.
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Heliyon 10 (2024) e32141

Contents lists available at ScienceDirect

Assessment of Helicobacter pylori cytotoxin-associated Gene A (Cag

2. Materials and methods

2.1. Study design, sample size and sample preparation

SD= Standard Deviation.

2.2. PREMIER H. pylori serum test

2.3. CagA ELISA test

2.4. Vitamin B12 ELISA test

2.5. Ferritin ELISA test

2.6. Statistical analysis

Negative, n = 551 Positive, n = 543

3.1. Socio-demographic profile of study participants

3.2. Assessment of H. pylori infection, CagA, vitamin B12 and ferritin

Negative, n = 225 Positive, n = 318

Fig. 5. Association of ferritin deficiency with H. pylori and CagA seropositivity.

Data availability Statement

CRediT authorship contribution statement

Declaration of competing interest

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