Sojourners visiting high-altitude (HA) (>2500 m) are susceptible to HA disorders;
on the contrary, HA natives are well adapted to the extreme hypoxic environment. High
aldosterone levels are believed to be involved in HA disorders, we, therefore, envisaged
role of CYP11B2 gene variants in HA adaptation and therefore investigated the -344T/C,
intron-2 conversion (Iw/Ic), K173R, and A5160C polymorphisms. In addition, polymorphisms
in AGT, AT1R, ATP1A1, ADRB2, and GSTP1 genes were also investigated. The study comprised
of 662 subjects, comprising of 426 Himalayan highlanders (HLs) and 236 lowlanders
(LLs). The -344T/C and K173R polymorphisms were found to be in complete linkage disequilibrium.
The wild-type allele -344T and combination of wild-type homozygous genotypes between
-344T/C, Iw/Ic, and A5160C polymorphisms, containing all the six wild-type alleles
were over-represented in the HLs (p < 0.0001, and p = 0.008, respectively). The wild-type
haplotypes -344T-Iw, -344T-5160A, and -344T-Iw-5160A also showed over-representation
in the HLs (p < 0.0001). Furthermore, greater the number of wild-type alleles, lower
was the ARR (p < 0.05). The genotype distribution in remaining genes did not differ.
To conclude, the over-representation of wild-type -344T allele, genotype combinations
and haplotypes of CYP11B2, and their correlation with lower aldosterone levels associate
with HA adaptation in the HLs. Such an allelic presentation in sojourners may help
them cope with adverse HA environment.