The impact of PPARγ and ApoE gene polymorphisms on susceptibility to diabetic kidney disease in type 2 diabetes mellitus: a meta-analysis

Background: Globally, diabetic kidney disease (DKD) has become the leading cause of end-stage renal disease, imposing substantial social and economic costs. This meta-analysis was designed to provide valuable insights into gene-disease interactions by investigating the potential association between lipid metabolism gene polymorphisms and the risk of DKD. Methods: An electronic literature search was conducted on MEDLINE Complete, Web of Science, Embase, and PubMed. A total of 18 studies on the peroxisome proliferator-activated receptor γ (PPARγ) Pro12Ala variant and 20 publications concerning apolipoprotein E (ApoE) gene polymorphism were included in the meta-analysis. Results: Overall, the PPARγ Pro12Ala polymorphism was found to be significantly associated with a decreased DKD risk (OR = 0.74, 95% CI: 0.62–0.88). In subgroup analysis, Ala carriers were less susceptible to DKD than Pro homozygotes among Asian (OR = 0.73, 95% CI: 0.56–0.95) and Caucasian populations (OR = 0.74, 95% CI: 0.59–0.93). Subgroup analysis stratified by albuminuria categories showed that the PPARγ Pro12Ala polymorphism reduced the risk of both microalbuminuria and macroalbuminuria with corresponding ORs of 0.58 (95% CI: 0.43–0.78) and 0.68 (95% CI: 0.53–0.86). Sensitivity analysis confirmed the robustness of the meta-analysis results. However, publication bias was identified in the subgroup analysis of the Caucasian population. The primary analysis of the ApoE gene polymorphism yielded significant findings, indicating that ApoE ε2/ε2, ApoE ε2/ε3, and ApoE ε2/ε4 genotypes increase the risk of DKD (ε2/ε2 vs. ε3/ε3: OR = 1.93, 95% CI: 1.03–3.61; ε2/ε3 vs. ε3/ε3: OR = 1.63, 95% CI: 1.19–2.25; ε2/ε4 vs. ε3/ε3: OR = 1.87, 95% CI: 1.37–2.55). However, sensitivity analysis suggested that influential and Hardy-Weinberg equilibrium (HWE)-violating studies may impact the overall effect estimates. Conclusions: A meta-analysis showed that PPARγ gene polymorphism may be a protective factor for DKD, whereas the ApoE ε2/ε2, ApoE ε2/ε3, and ApoE ε2/ε4 genotypes are associated with an increased risk of DKD. However, the role of ApoE gene polymorphism in susceptibility to DKD is less certain and requires further evaluation.