Polymorphism profiling of nine high altitude relevant candidate gene loci in acclimatized sojourners and adapted natives

BACKGROUND: Sea level sojourners, on ascent to high altitude, undergo acclimatization through integrated physiological processes for defending the body against oxygen deprivation while the high altitude natives (resident population) are adapted to the prevailing hypobaric hypoxic condition through natural selection. Separating the acclimatization processes from adaptive changes and identifying genetic markers in lowlanders that may be beneficial for offsetting the high altitude hypoxic stress, although challenging, is worth investigating. We genotyped nine candidate gene polymorphisms, suggested to be relevant in high altitude environment, in sea level acclimatized sojourners and adapted natives for understanding differences/commonality between the acclimatized and the adapted cohorts at the genetic level. RESULTS: Statistically similar genotypic and allelic frequencies were observed between the sea level sojourners (acclimatized) and the high altitude natives (adapted) in six loci viz., EDN1 (endothelin 1) -3A/-4A VNTR, ADRB2 (beta-2 adrenergic receptor, surface) Arg16Gly (rs1042713:A > G), ADRB3 (beta-3 adrenergic receptor) Trp64Arg (rs4994:T > C), eNOS (nitric oxide synthase, endothelial) Glu298Asp (rs1799983:T > G), TH (tyrosine hydroxylase) Val81Met (rs6356:G > A) and VEGF (vascular endothelial growth factor) 963C > T (rs3025039:C > T) while SCNN1B (amiloride-sensitive sodium channel, subunit beta) Thr594Met (rs1799979:C > T) was monomorphic. Genotypic and allelic frequencies in EDN1 9465G > A (rs2071942:G > A) and ADRB2 Gln27Glu (rs1042714:G > C) were significantly different between the acclimatized sojourners and the high altitude natives with higher frequency of GG and GA genotypes of EDN1 rs2071942 and CC genotype of ADRB2 rs1042714 being observed in Ladakh natives. Mutated A allele (AA genotype) of rs2071942 and carriers of G allele (GG + GC genotypes) of rs1042714 were less favorable during acclimatization under recessive and dominant genetic models of inheritance respectively indicating thereby that GG genotype and G allele of EDN1 rs2071942 and CC genotype of ADRB2 rs1042714 conferred acclimatization benefit. CONCLUSION: Sea level acclimatized individuals shared similarity with the adapted natives in certain high altitude relevant genetically based trait variation suggesting advantageous consequence as well as commonality in gene regulatory pathways in which these gene products function both during process of acclimatization and adaptation in high altitude environment. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12863-015-0268-y) contains supplementary material, which is available to authorized users.