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

BackgroundGlobally, 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.MethodsAn 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 gamma (PPAR gamma) Pro12Ala variant and 20 publications concerning apolipoprotein E (ApoE) gene polymorphism were included in the meta-analysis.ResultsOverall, the PPAR gamma 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 PPAR gamma 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 epsilon 2/epsilon 2, ApoE epsilon 2/epsilon 3, and ApoE epsilon 2/epsilon 4 genotypes increase the risk of DKD (epsilon 2/epsilon 2 vs. epsilon 3/epsilon 3: OR = 1.93, 95% CI: 1.03-3.61; epsilon 2/epsilon 3 vs. epsilon 3/epsilon 3: OR = 1.63, 95% CI: 1.19-2.25; epsilon 2/epsilon 4 vs. epsilon 3/epsilon 3: 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.ConclusionsA meta-analysis showed that PPAR gamma gene polymorphism may be a protective factor for DKD, whereas the ApoE epsilon 2/epsilon 2, ApoE epsilon 2/epsilon 3, and ApoE epsilon 2/epsilon 4 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.