Synergistic effects of gene polymorphisms of the renin-angiotensin-aldosterone system on essential hypertension in Kazakhs in Xinjiang

• Published in: Clinical and experimental hypertension (1993) 2016-01, Vol.38 (1), p.63-70
• Main Authors: Niu, Shudong, Zhang, Bin, Zhang, Keyong, Zhu, Pengcheng, Li, Jingping, Sun, Yujing, He, Ning, Zhang, Mingtao, Gao, Zhiying, Li, Xueyan, Simayi, Amuti, Ge, Jie, Cong, Mingyu, Zhou, Wenna, Qiu, Changchun
• Format: Article
• Language: English
• Subjects: Essential hypertension; haplotype; multifactor dimensionality reduction; renin-angiotensin-aldosterone system; Xinjiang Kazakh
• ISSN: 1064-1963; 1525-6006
• DOI: 10.3109/10641963.2015.1060985

Objective: To assess the synergistic effects of gene polymorphisms of the renin-angiotensin-aldosterone system (RAAS) on essential hypertension (EH) in Kazakhs in Xinjiang. Methods: A cross-sectional case-control association study was conducted in 52 1 hypertensive and 623 normotensive subjects of Kazakh ethnicity on eight common single nucleotide polymorphisms (SNPs) interspersed over five genes of the RAAS. SNPs were genotyped by polymerase chain reaction-restriction fragment length polymorphism. Interactions among the SNPs were analyzed by the multifactor dimensionality reduction method (MDR). Results: In single-locus analysis, subjects with AGT -6G, ACE D, and CYP11B2 -344C had increased susceptibility to EH (OR: 1.249; 1.425; 1.201). When subgrouped by sex, males with the t allele of REN Taq I had decreased risk for EH (OR: 0.529), and those with AGT -6G and CYP11B2 -344 C had increased risk for EH (OR: 1.498; 1.449). In females, carrying ACE D increased the risk for EH. (OR: 1.327). In six AGT haplotypes, H1 was protective, while H3 increased susceptibility to EH (OR: 0.683; 2.025). Interaction analysis by MDR showed that there was a strong synergistic effect between ACE I/D and CY11B2 (T-344C) and a moderate interaction between both ACE I/D and CY11B2 T-344C and AGT A-6G. Conclusions: There was a strong synergistic effect between ACE I/D and CY11B2 T-344C and a moderate effect between both ACE I/D and CY11B2 T-344C and AGT A-6G. AGT -6G, ACE D, and CY11B2 -344C increased susceptibility to EH. REN Taq I, AGT -6G, CY11B2 -344 C and ACE D were associated with male and female EH, respectively. H1 and H3 of AGT were protective and risk haplotypes, respectively.