Association between two genetic polymorphisms of the renin-angiotensin-aldosterone system and diabetic nephropathy: a meta-analysis.

The widely studied candidate genes of the renin-angiotensin-aldosterone system, angiotensinogen (AGT), and angiotensin II receptor type 1 (AGTR1), are implicated in the development of diabetic nephropathy (DN). A number of studies have evaluated the association between the functional polymorphisms, AGT M235T and AGTR1 A1166C, and DN risk with conflicting results. The present meta-analysis was performed to estimate the overall risk of these polymorphisms associated with DN on 4,377 DN cases and 4,905 controls from 34 published case–control studies by searching electronic databases and reference lists of relevant articles. We examined the association between each polymorphism and the risk of DN by odds ratio (OR) with 95% confidence intervals (95% CI) and calculated the ORs for different genetic model. In addition, stratification analysis by ethnicity and diabetes mellitus (DM) type was conducted. In this meta-analysis, we failed to find any significant main effects in both overall analysis and stratified analysis for the AGT M235T. However, the overall analysis detected a significant association between the AGTR1 A1166C and the risk of DN for the CC compared with the AA and dominant genetic model (CC vs. AA: OR = 2.10, 95% CI: 1.00–4.44; dominant model: OR = 2.11, 95% CI: 1.06–4.23). In subgroup analysis, only patients with T2DM showed significant association for CC vs. AA model and dominant model (CC vs. AA: OR = 3.31, 95% CI: 1.21–9.08; dominant model: OR = 3.50, 95% CI: 1.41–8.69). This study suggests that the AGTR1 A1166C polymorphism may contribute to DN development, particularly in T2DM patients.