Associations between the polymorphisms of main components in PI3K/Akt pathway and risk of diabetic kidney disease: A meta‐analysis.

Aims: Diabetic kidney disease (DKD) is a severe microvascular complication frequently associated with type 1 and type 2 diabetes mellitus. The objective of this work was to evaluate the relevance of PI3K/Akt pathway polymorphisms and DKD susceptibility by a meta‐analysis. Methods: Case–control studies related to the relationship between PI3K/Akt pathway polymorphisms and DKD risk were searched from Pubmed, Embase, Cochrane Library, SINOMED, CNKI, and Wanfang databases. Statistical analysis and heterogeneity test were conducted by Review Manager 5.4. Results: Totally, 52 eligible studies were enrolled, including seven single nucleotide polymorphisms (SNPs) for four genes in the PI3K/AKT pathway (GNB3: rs5443; eNOS: rs1799983, rs869109213, rs2070744; IL‐6: rs1800795, rs1800796; TNFα: rs1800629). The "M" allele of eNOS rs1799983 was related to the increased risk of DKD under random effects model, especially in Asian population (Overall:M vs. W: I2 = 75%, OR = 1.29, 95%CI 1.07–1.56; MM + WM vs. WW: I2 = 75%, OR = 1.50, 95%CI 1.21–1.86). The "M" allele of eNOS rs869109213 was implicated with higher prevalence of DKD under random effects model, especially in Asian population (Overall:M vs. W: I2 = 63%, OR = 1.43, 95%CI 1.22–1.68; MM + WM vs. WW: I2 = 50%, OR = 1.36, 95%CI 1.16–1.58; MM vs. WM + WW: I2 = 59%, OR = 2.20, 95%CI 1.41–3.43). The "M" allele of eNOS rs2070744 was implicated with higher prevalence of DKD under random effects model, especially in Indian population (Overall: M vs. W: I2 = 47%, OR = 1.35, 95%CI 1.15–1.59; MM + WM vs. WW: I2 = 45%, OR = 1.32, 95%CI 1.07–1.62; MM vs. WM + WW: I2 = 65%, OR = 2.29, 95%CI 1.39–3.77). The "M" allele of IL‐6 rs1800796 was predominately associated with higher DKD risks under random effects model, especially in Asian population (Overall: M versus W: I2 = 23%, OR = 1.49, 95%CI 1.21–1.84; MM + WM vs. WW: I2 = 1%, OR = 1.43, 95%CI 1.15–1.77; MM + WM vs. WW: I2 = 71%, OR = 2.77, 95%CI 1.09–7.06). Conclusions: This meta‐analysis indicated that polymorphisms in the PI3K/Akt pathway in eNOS rs1799983, rs869109213, rs2070744, and IL‐6 rs1800796 were related to the increased risk of DKD. [ABSTRACT FROM AUTHOR]