High Altitude Pulmonary Edema (HAPE) is a threatening disorder caused due to acute exposure to high altitude above 3000m. Apart from multiple factors involved, the genetic factors also play an important function in the pathogenesis of...
moreHigh Altitude Pulmonary Edema (HAPE) is a threatening disorder caused due to acute exposure to high
altitude above 3000m. Apart from multiple factors involved, the genetic factors also play an important
function in the pathogenesis of HAPE. This study aims to evaluate the role of mtDNA polymorphism
and their association with haplogroup in understanding the etiology of HAPE. In this study, all the
HAPE susceptible and acclimatized control subjects could be classifed into nine haplogroups pertaining
mostly to Macrohaplogroup M and U. The frequency of haplogroup M was signifcantly higher in HAPE
susceptibles whereas the haplogroup M33a2′3 was found only in HAPE susceptibles. The variant
G4491A and A4944G of MT-ND2, A14002G of MT-ND5, and C8562T of MT-ATP8, were defnition site of
haplogroup M33a2′3. The frequency of A10398G of MT-ND3, A8701G of MT-ATP6 and C14766T of MTCYB
genes were signifcantly higher in HAPE susceptibles. mtDNA copy number also plays a signifcant
synergistic role in HAPE susceptibility. Our fndings suggests that variants in MT-ND2 and MT-ND5 were
predicted to confer decreased protein stability in HAPE susceptibles and in particular, highly conserved
variants G4491A, A4944G and A14002G associated with haplogroup M33a2′3 may be the primary cause
of susceptibility to HAPE in Indian male lowlanders.
