Angiotensin II type 1 receptor polymorphisms and susceptibility to hypertension: a HuGE review

Abstract

The angiotensin II type 1 receptor (AGTR1) plays an integral role in blood pressure control, and is implicated in the pathogenesis of hypertension. Polymorphisms within this gene have been extensively studied in association with hypertension; however, findings are conflicting. To clarify these data, we conducted a systematic review of association studies of AGTR1 polymorphisms and hypertension, and performed a meta-analysis of the rs5186 variant. Results show that the currently available literature is too heterogeneous to draw meaningful conclusions. The definition of hypertension and gender composition of individual studies helps to explain this heterogeneity. Although the structure and splicing pattern of AGTR1 would suggest a likely effect of polymorphisms within the promoter region on gene function, few studies have been conducted thus far. In conclusion, there is insufficient evidence that polymorphisms in the AGTR1 gene are risk factors for hypertension. However, most studies are inadequately powered, and larger well-designed studies of haplotypes are warranted.

Fig. 1

A C, Forest plots for dominant, recessive, and additive genetic models of rs5186 polymorphism in association with hypertension, including all studies. (Dotted line represents null value.) Filled OR is the adjusted estimate using meta-bias to estimate results if publication bias were not present. (1A) Dominant Model: *heterogeneity χ² P = 0.08; τ² = 0.021; I² = 34%; Egger’s publication bias P = 0.51.†Heterogeneity χ² P = 0.09; τ² = 0.028;I² = 35%; Egger’s publication bias P = 0.75. (1B) Recessive Model:*heterogeneity χ² P = 0.08; τ² 0.074; I² = 34%; Egger’s publication bias P = 0.98.†Heterogeneity χ² P = 0.68; τ² = 0.000;I² = 0%; Egger’s publication bias P = 0.09; Asian summary OR: 0.99 (95%CI: 0.59, 1.68). (1C) Additive Model: *heterogeneity χ² P = 0.001; τ² = 0.040;I² =58%; Egger’s publication bias P = 0.47. †Heterogeneity χ² P = 0.15; τ² = 0.020;I² =28%; Egger’s publication bias P = 0.93; Asian summary OR: 1.07 (0.93, 1.23).