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  • Title: Association of polymorphisms in angiotensin and aldosterone synthase genes of the renin-angiotensin-aldosterone system with high-altitude pulmonary edema.
    Author: Srivastava S, Bhagi S, Kumari B, Chandra K, Sarkar S, Ashraf MZ.
    Journal: J Renin Angiotensin Aldosterone Syst; 2012 Mar; 13(1):155-60. PubMed ID: 22156739.
    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.
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