Combined Action of ACE Gene I/D and GNB3 Gene C825T Polymorphisms on Essential Hypertension in Northern Han Chinese
- VernacularTitle:在中国北方汉族人群中血管紧张素转换酶基因I/D多态与G蛋白beta3亚基基因C825T多态对原发性高血压的联合作用
- Author:
Wentao HUANG
;
Hongjiang YU
;
Xiangfeng LU
;
Weiyan ZHAO
;
Yuelan WANG
;
Dongfeng GU
;
Runsheng CHEN
- Publication Type:Journal Article
- Keywords:
angiotensin-converting enzyme;
G-protein beta3 subunit;
interaction;
combination effect;
hypertension
- From:
Progress in Biochemistry and Biophysics
2007;34(5):471-478
- CountryChina
- Language:Chinese
-
Abstract:
Essential hypertension (EH), a complex polygenic disease, is considered to the result of the genetic interaction of multiple gene alterations in concert with environmental factors. Evidences showed that angiotensin-converting enzyme (ACE) gene and G protein beta3 subunit (GNB3) gene are both important susceptibility genes for EH, and that there exists putative biological connection between the two genes in developing hypertension. To investigate whether hypertension was affected by gene-gene interaction between the two genes in the northern Chinese Han population, a case-control association study including 502 hypertensive cases and 490healthy controls was conducted, selecting the ACE gene I/D polymorpinsm and the GNB3 gene C825T polymorphism. Linkage disequilibrium analysis revealed a significant nonrandom distribution only in male hypertensives, indicating that interaction between ACE gene and GNB3 gene may predispose males to the occurrence of hypertension. Multivariate stepwise logistic regression in single locus analysis, with adjustment for common risk factors for hypertension, demonstrated that the OR for DD/ID versus Ⅱ for hypertension among men was significant (OR 1.57; 95% CI, 1.09 ~2.27; P = 0.016) in dominant genetic model. In combination analysis stratified with respect to gender, slightly significant ORs were found after adjustment in males: OR for TT vs CC, 0.11; 95%CI, 0.01 ~0.99; P = 0.049 within ACE DD genotype; OR for DD/ID vs Ⅱ, 1.52; 95% CI, 1.01 ~2.29; P = 0.047 within GNB3 CC+CT genotype. The results suggest that ACE, or a nearby gene, is a male-specific susceptible gene for hypertension, and that there may exist epistatic gene-gene interaction between ACE D allele and GNB3 825C allele.