Abstract
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.