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

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.

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.

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.

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.

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.