Genetic association of ACE gene I/D polymorphism with the risk of diabetic kidney disease; a meta-analysis

Introduction: Diabetic nephropathy (DN) is a progressive renal disease characterized by persistent albuminuria that leads to end-stage renal disease in both type 1 diabetes (T1DM) and type 2 diabetes (T2DM) patients. The renin-angiotensin-aldosterone system (RAAS) plays a major role in the onset and progression of DN. Objectives: The present meta-analysis is intended to synthesize evidence on the association between ACE gene insertion and deletion (ACE I/D) polymorphism and the risk of DN. Methods: PubMed, Scopus, Google Scholar and Embase were searched to retrieve relevant publications. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to evaluate the association between ACE I/D polymorphism and DN risk. The Cochrane Q test and I2 statistic were used to detect heterogeneity. To assess between-study heterogeneity, subgroup analysis and sensitivity analysis were performed. Funnel plots and Egger’s test were used to estimate publication bias. Results: Around 45 articles (47 studies) with 6124 patients of DN and 2492 T2DM patients (controls) were ultimately considered for meta-analysis. Overall, the ACE I/D polymorphism was associated with DN under three different genetic models (allelic model: OR = 1.34; 95% CI: 1.20- 1.49; P<0.001; dominant model: OR= 1.54; 95% CI: 1.31- 1.81; P<0.001; and recessive model: OR= 1.39; 95% CI: 1.19- 1.63; P<0.001). Significant heterogeneity (I2 > 50%) was present in the analysis for all ethnic groups. Further, there is no evidence for publication bias in this meta-analysis. Conclusion: The current meta-analysis provided confirmation that the ACE I/D polymorphism is correlated with an increased risk of DN in patients with T2DM and the D allele of ACE I/D was a susceptible factor.