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- Title
Synergistic effect of the genetic polymorphisms of the renin–angiotensin–aldosterone system on high-altitude pulmonary edema: a study from Qinghai-Tibet altitude.
- Authors
Yue Qi; Wenquan Niu; Tongchun Zhu; Wenyu Zhou; Changchun Qiu
- Abstract
Abstract The pathogenesis of high-altitude pulmonary edema (HAPE) has been at least partially attributed to the local dysregulation of the renin–angiotensin–aldosterone system (RAAS) cascade. To address this issue, we conducted the largest nested case-control study to-date to explore the association between variations in RAAS genes and HAPE in Chinese population. We recruited 140 HAPE patients and 144 controls during the construction of Qinghai-Tibet railway and genotyped 10 gene polymorphisms evenly interspersed in 5 RAAS candidate genes. The data were analyzed by haplotype and multifactor dimensionality reduction (MDR). The single-locus analysis showed that CYP11B2 C-344T and K173R and ACE A-240T polymorphisms were significantly associated with HAPE after Bonferroni correction (P P = 0.004). The homozygous genotype combination of −240AA, 2350GG and −344TT conferred high genetic susceptibility to HAPE, which was further strengthened by haplotype analysis. Our results add evidence for synergistic effect of RAAS gene polymorphisms on HAPE susceptibility. Moreover, we proposed a promising data-mining analytical approach (MDR) for detecting and characterizing gene-gene interactions.
- Subjects
CHINA; GENETIC polymorphisms; RENIN-angiotensin system; PULMONARY edema
- Publication
European Journal of Epidemiology, 2008, Vol 23, Issue 2, p143
- ISSN
0393-2990
- Publication type
Article
- DOI
10.1007/s10654-007-9208-0