Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0034063 (pulmonary edema)
 10,665 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The genes of the renin--angiotensin system (RAS) play an important role in the regulation of pulmonary vascular tone. Although studies on individual genes polymorphisms have reported association with high-altitude pulmonary oedema (HAPE), studies on multiple genes or epistasis are lacking. We therefore investigated the association of the RAS polymorphisms with HAPE. In a case-control design, we screened 163 HAPE-resistant/controls (HAPE-r) and 160 HAPEpatients (HAPE-p) of Indian origin for eight polymorphisms of four RAS genes, ACE, AGT, AGTR1 and AGTR2. Significant difference in genotype and allele frequencies of the ACE I/D and AGT M235T polymorphisms was observed between HAPE-p and HAPE-r (p < 0.05). In three-locus haplotype analysis of AGT the haplotype GTM was significantly higher in HAPE-p (29%) and haplotype GTT in HAPE-r (27%) after Bonferroni correction (p < 0.006). The differences were insignificant for polymorphisms from AGTR1 and AGTR2. The MDR (multifactor dimensional reduction) approach for gene--gene interaction depicted individual polymorphism M235T as the best disease predicting model (cross validation consistency, CVC = 10/10). We found a significant association of D allele of ACE and M allele of AGT with HAPE. The findings are supported at the haplotypic level as well as through nested genetic interaction between the RAS gene polymorphisms using the MDR approach.
J Renin Angiotensin Aldosterone Syst 2011 Jun
PMID:Polymorphisms of renin--angiotensin system genes as a risk factor for high-altitude pulmonary oedema. 2139 62

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.
J Renin Angiotensin Aldosterone Syst 2012 Mar
PMID:Association of polymorphisms in angiotensin and aldosterone synthase genes of the renin-angiotensin-aldosterone system with high-altitude pulmonary edema. 2215 39