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Associations between the polymorphisms of main components in PI3K/Akt pathway and risk of diabetic kidney disease: A
Hang Fu1,2, Congcong Guo2, Jing Zhang3
1First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, China.
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.
Insights
This meta-analysis found that specific polymorphisms in the PI3K/Akt pathway, particularly in eNOS and IL-6 genes, are linked to an increased risk of diabetic kidney disease (DKD). These genetic variations may contribute to DKD susceptibility in diabetic patients.
Area of Science:
- Genetics and Molecular Biology
- Nephrology
- Endocrinology
Background:
- Diabetic kidney disease (DKD) is a serious complication of diabetes, significantly increasing morbidity and mortality.
- The phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) pathway plays a crucial role in cellular processes relevant to DKD pathogenesis.
- Understanding the genetic underpinnings of DKD susceptibility is vital for developing targeted prevention and treatment strategies.
Approach:
- A comprehensive meta-analysis was conducted, systematically searching major scientific databases for relevant case-control studies.
- Fifty-two eligible studies encompassing seven single nucleotide polymorphisms (SNPs) across four genes (GNB3, eNOS, IL-6, TNFα) within the PI3K/Akt pathway were included.
- Statistical analyses, including heterogeneity testing, were performed using Review Manager 5.4 to synthesize the findings.
Key Points:
- Polymorphisms in eNOS (rs1799983, rs869109213, rs2070744) and IL-6 (rs1800796) within the PI3K/Akt pathway were significantly associated with an increased risk of DKD.
- The 'M' allele of eNOS rs1799983 showed a 29% increased DKD risk overall and a 50% increase in the Asian population.
- The 'M' allele of IL-6 rs1800796 was predominantly associated with higher DKD risks, particularly in the Asian population, with a 49% increased risk overall.
Conclusions:
- Specific PI3K/Akt pathway gene polymorphisms, notably in eNOS and IL-6, are implicated as risk factors for developing diabetic kidney disease.
- These genetic associations highlight the PI3K/Akt pathway's role in DKD pathogenesis and suggest potential targets for future research.
- The findings underscore the importance of considering genetic predisposition in the context of diabetes management and DKD prevention.
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