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Oxygen sensing pathway: genetic adaptation at high‐altitude
Author(s) -
Pasha MA Qadar,
Mishra Aastha,
Mohammad Ghulam
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.897.1
Subject(s) - allele , biology , genetics , gene , genome wide association study , population , microbiology and biotechnology , genotype , medicine , single nucleotide polymorphism , environmental health
Residents of Himalayas have evidence of selection of genetic variants and the genes of oxygen sensing pathway have emerged favorite candidates. Candidate gene and genome‐wide association studies (GWAS) have substantiated the involvement of endothelial PAS domain‐containing protein 1 (EPAS1) and HIF‐1 prolyl hydroxylase 2 (EGLN1) in adaptation to and disorders of hypobaric hypoxia. The case‐control design enumerated the selection of EGLN1 T allele of rs480902 and C allele of rs479200 in HA population (P=4.01E‐07). Conversely, the variants were overrepresented in HAPE (P<0.05). Other two candidates of this pathway namely endothelial nitric oxide synthase ( NOS3) and endothelin‐1 ( ET‐1) also associated. The alleles 298Glu of 298Glu/Asp and 4b of 4b/4a polymorphisms of NOS3 , G of 2288G/T polymorphism and longer‐repeats of (CT)n–(CA)n repeat of ET‐1 were overrepresented in natives (P≤0.05); whereas, alleles 298Asp, 4a, T, and shorter‐repeats of respective gene polymorphisms were associated with HAPE (P≤0.05). Plasma NO, ET‐1 levels differentially associated with the variants. These studies clearly demonstrate the evolutionary selection of genetic variants in Tibetans that helped them achieve physiological profile similar to normoxic condition. This work was funded by Council of Scientific and Industrial Research, India.