The EDN1 Missense Variant rs5370 G > T Regulates Adaptation and Maladaptation under Hypobaric Hypoxia

Tsering Palmo, Bilal Ahmed Abbasi, Neha Chanana, Kavita Sharma, Mohammed Faruq, Tashi Thinlas, Malik Z. Abdin () and Qadar Pasha ()
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Tsering Palmo: Genomics and Molecular Medicine, CSIR-Institute of Genomics and Integrative Biology, Delhi 110007, India
Bilal Ahmed Abbasi: Genomics and Molecular Medicine, CSIR-Institute of Genomics and Integrative Biology, Delhi 110007, India
Neha Chanana: Genomics and Molecular Medicine, CSIR-Institute of Genomics and Integrative Biology, Delhi 110007, India
Kavita Sharma: Genomics and Molecular Medicine, CSIR-Institute of Genomics and Integrative Biology, Delhi 110007, India
Mohammed Faruq: Genomics and Molecular Medicine, CSIR-Institute of Genomics and Integrative Biology, Delhi 110007, India
Tashi Thinlas: Sonam Norboo Memorial Hospital, Leh 194101, Ladakh, India
Malik Z. Abdin: Department of Biotechnology, Jamia Hamdard, New Delhi 110062, India
Qadar Pasha: Genomics and Molecular Medicine, CSIR-Institute of Genomics and Integrative Biology, Delhi 110007, India

IJERPH, 2022, vol. 19, issue 18, 1-13

Abstract: Endothelin 1 ( EDN1 ) encodes a potent endogenous vasoconstrictor, ET1, to maintain vascular homeostasis and redistribution of tissue blood flow during exercise. One of the EDN1 missense polymorphisms, rs5370 G/T , has strongly been associated with cardiopulmonary diseases. This study investigated the impact of rs5370 polymorphism in high-altitude pulmonary oedema (HAPE) disorder or maladaptation and adaptation physiology in a well-characterized case–control study of high-altitude and low-altitude populations comprising 310 samples each of HAPE-patients, HAPE-free controls and native highlanders. The rs5370 polymorphism was genotyped, and the gene expression and plasma level of EDN1 were evaluated. The functional relevance of each allele was investigated in the human embryonic kidney 293 cell line after exposure to hypoxia and computationally. The T allele was significantly more prevalent in HAPE-p compared to HAPE-f and HLs. The EDN1 gene expression and ET1 bio-level were significantly elevated in HAPE-p compared to controls. Compared to the G allele, the T allele was significantly associated with elevated levels of ET-1 in all three study groups and cells exposed to hypoxia. The in silico studies further confirmed the stabilizing effect of the T allele on the structural integrity and function of ET1 protein. The ET1 rs5370 T allele is associated with an increased concentration of ET-1 in vivo and in vitro, establishing it as a potent marker in the adaptation/maladaptation physiology under the high-altitude environment. This could also be pertinent in endurance exercises at high altitudes.

Keywords: high altitude; hypobaric hypoxia; adaptation; endurance; maladaptation; high-altitude pulmonary oedema; endothelin 1; vascular homeostasis (search for similar items in EconPapers)
JEL-codes: I I1 I3 Q Q5 (search for similar items in EconPapers)
Date: 2022
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