Papers by Gorana Stamenkovic
Archives of Biological Sciences, 2007
Virus Evolution, Dec 22, 2022

Genetika, 2017
Methylenetetrahydrofolate reductase (MTHFR) plays a critical role in the folate metabolism. The p... more Methylenetetrahydrofolate reductase (MTHFR) plays a critical role in the folate metabolism. The polymorphism 677C>T of the MTHFR gene, producing thermolabile enzyme with decreased function, is widely studied and associated with many conditions. Additionally, it has been shown that another polymorphism, 1298A>C, also reduces the activity of this enzyme, although to a lesser extent. The aim of this study is to evaluate the clinical informativeness of testing both MTHFR polymorphisms. Genomic DNA, were extracted from peripheral blood of 180 female patients with pregnancy complications and 183 healthy female controls, and genotyped for MTHFR 677C>T and 1298A>C loci, using TaqMan assays. Our study found similar frequency of alleles and genotypes between two groups. Based on MTHFR 677C>T genotype, 11.7% of patients homozygous for this mutation were under the possible risk. When the position 1298 was included in the testing, 22.8% of the patients were heterozygous for both p...

Human Fertility, 2018
Unexplained infertility refers to the absence of a definable cause of reproductive failure. Vitam... more Unexplained infertility refers to the absence of a definable cause of reproductive failure. Vitamin D receptor (VDR) acts as a transcription factor and regulates a number of vitamin D-responsive genes, including those involved in the immune system. Recent finding that VDR is expressed in reproductive tissues suggests a possible importance of vitamin D in pregnancy. We conducted a case-control study to examine the association of polymorphisms in VDR gene with reproductive success. DNA from 117 female patients with unexplained infertility and 130 fertile controls was isolated from peripheral blood and VDR genotypes (FokI, BsmI, ApaI and TaqI) were detected by PCR-RFLP. Haplotypes were determined using Haploview software. Our results show significant association of FokI and BsmI polymorphisms with infertility (p < 0.05). The haplotype analysis confirmed strong linkage disequilibrium between closely positioned BsmI, ApaI and TaqI polymorphisms. Two haplotypes were associated with infertility: (i) haplotype bAT was increasing the risk for secondary infertility; while (ii) haplotype BAT had a protective role against primary infertility (p < 0.05). By changing the expression and the activity of VDR gene, which leads to the change in expression of vitamin D-responsive genes, these polymorphisms and haplotypes could possibly have an effect on immune system in the female reproductive tract.

Blood Coagulation & Fibrinolysis, 2019
A numerous factor can cause infertility, but around one of four reproductive failure cases remain... more A numerous factor can cause infertility, but around one of four reproductive failure cases remain unexplained and diagnosed as idiopathic infertility. In the past few decades, analysis of gene polymorphisms takes a significant place in pathogenesis of infertility. The aim of this study was to evaluate the possible role of hemostasis-related gene polymorphisms in unexplained infertility. The study includes 117 female patients with idiopathic infertility and 130 fertile women with at least one born child. Eight polymorphisms important for hemostasis (ITGB3 1565T>C, FV 1691G>A, FII 20210G>A, MTHFR 677C>T and 1298A>C, ATIII 786G>A, PAI-14G/5G and ACE I/D) were genotyped by real-time PCR system. The frequencies of alleles and genotypes of examined polymorphisms were analyzed in SPSS statistical program, whereas gene interactions were identified using the GMDR software. Examination of etiological factors has shown that family history is a significant factor in assessing individual risk for infertility. The alleles and genotypes frequency of FV 1691G>A and FII 20210G>A polymorphisms were statistically different between control and patient group leading to a greater risk for infertility. The analysis of epistatic relationship between examined hemostasis-related gene polymorphisms identified more complex high-risk genotypes associated with infertility. Our results suggest that positive family history could be important predictive factor for fertility problems, pointing to the potential hereditary basis of this condition. Polymorphisms FVL and FII prothrombin are independent risk factors for idiopathic infertility, whereas multilocus interactions approach should be taken into consideration for the future research. Blood Coagul Fibrinolysis 30:253-262

Journal of Infection and Public Health, 2019
Background: Hantaviruses are etiological agents of emerging zoonotic diseases worldwide, includin... more Background: Hantaviruses are etiological agents of emerging zoonotic diseases worldwide, including hemorrhagic fever with renal syndrome (HFRS). A number of hantavirus species is known to be present in Europe. In Serbia, existing data on hantavirus presence and prevalence rely in serological findings. In this study, molecular analysis was performed in order to characterize HFRS causing hantaviruses in Serbia. Methods: Sixty four serum samples of HFRS cases, previously found seropositive to anti-hantaviral antibodies, were included in the study. Partial hantaviral L and S segments were PCR amplified producing 390nt and 598nt amplicons, respectively, in parallel with human beta-actin mRNA as external reverse transcription positive control. Hantavirus specific PCR products were DNA sequenced in both direction and the obtained sequences phylogenetically confirmed and analyzed. Results: PCR detection of hantavirus L and S genome segments was positive in 18/64 and 11/64 tested samples, respectively. Positive PCR results involved samples obtained from different locations, mostly from central and southern parts of Serbia. All the obtained sequences were identified as Dobrava-Belgrade virus (DOBV). In the phylogenetic analysis sequences from Serbia tended to cluster in distinctive, geographically related clusters. Conclusions: Our findings indicate DOBV as the main HFRS causing hantavirus in Serbia, the site of its initial isolation.
International Journal of Infectious Diseases, 2019

Human Fertility, 2016
Reproductive failure (recurrent foetal loss, unexplained infertility and IVF implantation failure... more Reproductive failure (recurrent foetal loss, unexplained infertility and IVF implantation failure) may be, in a number of cases, explained by thrombophilia, either acquired or inherited. Several genes contribute to thrombophilia, some with major effect (Factor V, Factor II), and some with minor effect (MTHFR, PAI-1, ATIII, etc.). The aim of this study was to estimate frequency of thrombophilia-associated genotypes (FII20210G > A, FV1691G > A, MTHFR677C > T and PAI-1-675 4G/ 5G) in a group of 1631 Serbian women experiencing reproductive failure, and compare it with a healthy, female control group. Our results showed marginally significant (p ¼ 0.050) differences in allele frequencies between patients and controls for the FV1691 mutations. For the FII20210G > A, although the statistical significance was not achieved (p ¼ 0.076), we found higher frequency of variant allele in patients compared to controls (1.87% vs. 0.38%, respectively) which may point to a possible role of this polymorphism in thrombotic events. For the MTHFR677C > T and PAI-1-675 4G/5G, we found no difference in distributions of genotype or allele frequencies between these two groups (p > 0.05). For three subjects with very rare genotypes (two patients homozygous for FV1691G > A and one patient homozygous for FII20210G > A) we performed additional biochemical analyses for haemostasis, as well as genotyping of two polymorphisms (MTHFR1298A > C and ATIII786G > A).
Purpose: Bats have recently been recognized as potential reservoir of emerging human pathogens, i... more Purpose: Bats have recently been recognized as potential reservoir of emerging human pathogens, including hantaviruses and paramyxoviruses. Hantaviruses are known to be endemically present in Serbia, both in humans and in animal reservoirs comprising several rodent species, and causing hemorrhagic fever with renal syndrome. On the 4 other hand, paramyxoviruses are widely distributed worldwide and known to be associated with a range of human diseases (bronchiolitis, pneumonia, encephalitis, meningitis, parotitis, orchitis). No molecular data exist about the occurrence of human or zoonotic viruses in bats in Serbia. Aim: To examine the presence of paramyxovirus and hantavirus genetic material in bats in Serbia.
Archives of Biological Sciences, 2014
The Dobrava-Belgrade virus (DOBV) is a member of the Bunyaviridae family, genus Hantavirus, posse... more The Dobrava-Belgrade virus (DOBV) is a member of the Bunyaviridae family, genus Hantavirus, possessing a single-stranded RNA genome consisting of three segments, designated L (large), M (medium) and S (small). In this study, we present phylogenetic analysis of a newly detected DOBV strain isolated from Apodemus agrarius. Analysis was based on partial L and S segment sequences, in comparison to previously published DOBV sequences from Serbia and elsewhere. A phylogenetic tree based on partial S segment revealed local geographical clustering of DOBV sequences from Serbia, unrelated to host (rodent or human). The topology of the phylogenetic tree was confirmed with a high percent of completely or partially resolved quartets in likelihood-mapping analysis, whereas no evidence of possible recombination in the examined S segment data set was found.

Epidemiology and Infection, 2014
SUMMARYHantaviruses are endemic in the Balkans, particularly in Serbia, where sporadic cases and/... more SUMMARYHantaviruses are endemic in the Balkans, particularly in Serbia, where sporadic cases and/or outbreaks of hantaviral human disease have been reported repeatedly, and evidenced serologically. Here, we present genetic detection of Dobrava-Belgrade virus (DOBV) hantaviral sequences in wild rodents trapped in central Serbia. All the animals were pre-screened serologically by indirect immunofluorescence (IF) test and only those with a positive finding of hantaviral antigens were further tested by polymerase chain reaction. Of the total of 104 trapped animals, 20 were found to be IF positive and of those three were positive for hantaviral RNA: one Microtus arvalis for Tula virus, and one each of Apodemus agrarius and Glis glis for DOBV. Phylogenetic analysis of the obtained sequences implies putative DOBV spillover infection of A. agrarius and G. glis from Apodemus flavicollis. However, future investigations should help to identify the most common natural host and geographical dist...

Frontiers in Microbiology
BackgroundUsutu virus (USUV) is an emerging mosquito-borne Flavivirus, with birds as the main zoo... more BackgroundUsutu virus (USUV) is an emerging mosquito-borne Flavivirus, with birds as the main zoonotic reservoir. Humans are accidental hosts and mostly develop mild or even asymptomatic infections, although severe complications such as encephalitis can also arise. Detailed characterization of the pathogen's phylogenetics may offer valuable insights into the prediction and prevention of potential epidemics; however, lack of uniformity and the number of available USUV sequences worldwide hamper comprehensive investigation.AimThe study aimed to investigate USUV spatio-temporal dispersal inter- and intracontinentally and to estimate the dynamics of viral spread within Europe.MethodsPhylogeographic and phylodynamic analyses were done using advanced phylogenetic methods implemented in Beast 1.10.4 and Beast 2.6.4 software packages.ResultsHerein, we report on a new USUV isolate from Culex pipiens collected in 2019 from Serbia. The results of this research revealed two newly described ...
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Papers by Gorana Stamenkovic