title: 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.
authors.affiliation: Genomics Group, Defence Institute of Physiology and Allied Sciences, Delhi, India. genomics.dipas@gmail.com
authors.forename: Swati
authors.initials: S
authors.lastname: Srivastava
authors.forename: Shuchi
authors.initials: S
authors.lastname: Bhagi
authors.forename: Babita
authors.initials: B
authors.lastname: Kumari
authors.forename: Khem
authors.initials: K
authors.lastname: Chandra
authors.forename: Soma
authors.initials: S
authors.lastname: Sarkar
authors.forename: Mohammad Z
authors.initials: MZ
authors.lastname: Ashraf
mesh_terms: D000328:Adult; D000532:Altitude Sickness / Q000201:enzymology / Q000235:genetics*; D000809:Angiotensins / Q000235:genetics*; D019405:Cytochrome P-450 CYP11B2 / Q000235:genetics*; D004843:Epistasis, Genetic; D005787:Gene Frequency / Q000235:genetics; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D006976:Hypertension, Pulmonary / Q000201:enzymology / Q000235:genetics*; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics; D012084:Renin-Angiotensin System / Q000235:genetics*
chemical_list: C544065:AGTR1 protein, human; D000809:Angiotensins; D044140:Receptor, Angiotensin, Type 1; D019405:Cytochrome P-450 CYP11B2