ϵ2 allele and ϵ2-involved genotypes (ϵ2/ϵ2, ϵ2/ϵ3, and ϵ2/ϵ4) may confer the association of APOE genetic polymorphism with risks of nephropathy in type 2 diabetes: A meta-analysis

Abstract

Background: Diabetic nephropathy (DN) contributes to end-stage renal failure. Microvascular injury resulted from reactive oxygen species is implicated in the pathogenesis of DN. Genetic polymorphism of Apolipoprotein E (APOE) influences the antioxidative properties of the protein. The relationship of APOE polymorphism with the risks of nephropathy in type 2 diabetes (T2DN) remains elusive. Methods: An up-to-date meta-analysis was conducted on the basis of studies selected from PubMed, WanFang database, Embase, Vip database, Web of Science, Scopus, and CNKI database. Results: A total of 33 studies conferring 3266 cases and 3259 controls were selected on the basis of criteria of inclusion and exclusion in this meta-analysis. For APOE alleles, the pooled odds ratio (OR) of ϵ2 vs. ϵ3 was 1.89 (95% confidence intervals [95% CI]: 1.49-2.38, P < 0.0001). With regard to APOE genotypes, ϵ2/ϵ2, ϵ2/ϵ3, and ϵ2/ϵ4 increased the risk of T2DN (ϵ2/ϵ2 vs. ϵ3/ϵ3: OR = 2.32, 95% CI: 1.52-3.56, P = 0.0001; ϵ2/ϵ3 vs. ϵ3/ϵ3: OR = 1.97, 95% CI: 1.50-2.59, P<0.0001; ϵ2/ϵ4 vs. ϵ3/ϵ3: OR = 1.69, 95% CI: 1.18-2.44, P = 0.0046). Conclusions: This meta-analysis found that the APOE ϵ2 allele and the ϵ2-involved genotypes (ϵ2/ϵ2, ϵ2/ϵ3, and ϵ2/ϵ4) are the risk factors of T2DN.