Predominance of interaction among wild-type alleles of CYP11B2 in Himalayan natives associates with high-altitude adaptation

Rajput, Charu; Arif, Ehtesham; Vibhuti, Arpana; Stobdan, Tsering; Khan, Amjad P.; Norboo, Tsering; Afrin, Farhat; Pasha, M. A. Qadar

doi:10.1016/j.bbrc.2006.07.116

Cited by 23 publications

(22 citation statements)

References 31 publications

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“…Lower levels of aldosterone synthase, and consequently aldosterone, point towards a selective advantage at high altitude. 12 Also, highaltitude-induced dieresis is associated with marked changes in sodium and water-regulating hormones which are regulated by the RAAS, 13 thereby playing an important role in regulating vascular tone in HAPE. 14 We hypothesized that inter-individual differences in the genes of the RAAS pathway could be the genetic basis of susceptibility to HAPE.…”

Section: Introductionmentioning

confidence: 99%

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

Srivastava

Bhagi

Kumari

et al. 2011

J Renin Angiotensin Aldosterone Syst

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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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Section: Introductionmentioning

confidence: 99%

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

Srivastava

Bhagi

Kumari

et al. 2011

J Renin Angiotensin Aldosterone Syst

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“…In a study on Andean Quechua, G allele at the G894T polymorphism in NOS3, suggested to be beneficial in hypoxic environments, was more frequent compared to lowland Amerindians [80], while the frequency of the same allele was low in Nepalese population who suffered from AMS [79]. In the Himalayan Ladakhi population, allele 5160A of CYP11B2 was less frequent compared to Indian lowlanders [65] and the same allele was also shown to be associated with HAPE [61]. EPAS1 along with other genes in HIF pathway was studied in CMS in Andeans although no association was reported [51].…”

Section: Genetic Basis For Altitude Illnessmentioning

confidence: 87%

High-Altitude Medicine: The Path from Genomic Insight to Clinical Applications

Sarkar

2014

Translational Research in Environmental and Occupational Stress

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Translation of research findings into clinical practice is an important aspect of medical progress. In context of high-altitude medical research, understanding the functions of all genes and their regulation under highaltitude environment is far from complete, and translation of genomics research findings into clinical practice is yet an unexplored domain. With advancement and accessibility to genomic and genomewide data sets, understanding of the role of genes and environment under high altitude will get accelerated which can potentially get converted to translational research.

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“…Therefore, the results of the -344T>C polymorphism on MetS remain inconclusive. In previous studies (19)(20)(21)(22), the -344T>C and K173R polymorphisms were found strong in LD. Polymorphisms CYP11B2, K173R and -344T>C of this study exhibited a moderate level of LD.…”

Section: Discussionmentioning

confidence: 99%

Association of CYP11B2 polymorphisms with metabolic syndrome patients

Kim

Kang

et al. 2014

Biomedical Reports

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Abstract. Aldosterone synthase is a key enzyme in aldosterone production. Polymorphisms of the aldosterone synthase gene, CYP11B2, have been suggested to be involved in the pathogenesis of diabetes mellitus (DM), hypertension and cardiovascular diseases. In the light of these findings, we hypothesized that CYP11B2 genetic polymorphisms play a role in metabolic syndrome (MetS). Therefore, we investigated the associations of three CYP11B2 polymorphisms [-344T>C, K173R and intron 2 conversion (IC)] with Korean MetS patients. In total, 640 subjects comprising 320 cases and 320 control individuals) were included in the present study. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) techniques were used to assess CYP11B2 polymorphisms. The CYP11B2 -344T>C, K173R and IC polymorphisms did not exhibit a significant difference in the genotype and allele frequencies between the MetS and control groups. However, the -344T>C polymorphism in males and haplotypes comprising the three polymorphisms were associated with susceptibility to MetS. Thus, the pattern of haplotype associations was gender-specific. Based on these results, the -344T>C polymorphism in males and haplotypes of the CYP11B2 gene potentially affect MetS susceptibility. These findings remain to be confirmed in various ethnic populations with a larger sample size.

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Predominance of interaction among wild-type alleles of CYP11B2 in Himalayan natives associates with high-altitude adaptation

Cited by 23 publications

References 31 publications

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

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

High-Altitude Medicine: The Path from Genomic Insight to Clinical Applications

Association of CYP11B2 polymorphisms with metabolic syndrome patients

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