Association of polymorphisms in angiotensin and aldosterone synthase genes of the renin–angiotensin–aldosterone system with high-altitude pulmonary edema

Abstract

Studies on different populations have suggested variability in individual susceptibility to altitude sickness depending on genetic makeup. The renin–angiotensin–aldosterone system (RAAS) pathway plays a key role in regulation of vascular tone and circulatory homeostasis. The present study was undertaken to investigate the possible association of the RAAS in the development of high-altitude pulmonary edema (HAPE) in lowlanders exposed to high altitude. Three categories of subjects were selected: individuals who developed HAPE on acute induction to high altitude (HAPE); individuals tolerant to high-altitude exposure who showed no symptoms of HAPE (resistant controls; rCON); and natives of high altitude (HAN). Genetic variants in the genes of the RAAS such as renin (REN), angiotensin (AGT), angiotensin-converting enzyme (ACE), aldosterone synthase (CYP11B2) and angiotensin II receptor type 1 (AGTR1) have been investigated. The T174M polymorphism in AGT showed a significant difference in HAPE and HAN and also HAN and controls. Also, genotyping in the CYP11B2 T-344C promoter region resulted in a significant difference between HAPE and HAN both at genotypic and allelic levels. The genotypic difference was statistically insignificant for the AGTR1 A1166C 3’ UTR. The present investigation demonstrates a possible association between the polymorphisms existing in the RAAS pathway T174M and CYP11B2 C-344T and sensitivity of an individual to develop HAPE. The results also indicate the existence of ethnic variation between the HAN and the other two groups comprising lowlanders.

Keywords

Aldosterone synthase angiotensin gene polymorphism high-altitude pulmonary edema renin–angiotensin–aldosterone system

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