Affiliation:
1. First Clinical Medical College Shandong University of Traditional Chinese Medicine Jinan China
2. Department of Endocrinology and Metabology, Shandong Key Laboratory of Rheumatic Disease and Translational Medicine, Shandong Institute of Nephrology The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital Jinan China
3. School of Clinical Medicine Weifang Medical University Weifang China
4. Department of Endocrinology and Metabology, Shandong Provincial Qianfoshan Hospital, Shandong Key Laboratory of Rheumatic Disease and Translational medicine, Shandong Institute of Nephrology Cheeloo College of Medicine, Shandong University Jinan China
Abstract
AbstractAimsDiabetic 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.MethodsCase–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.ResultsTotally, 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).ConclusionsThis 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.
Funder
National Natural Science Foundation of China
Natural Science Foundation of Shandong Province
Subject
Cell Biology,Clinical Biochemistry,Genetics,Molecular Biology,Biochemistry