Methylenetetrahydrofolate reductase genetic polymorphism and the risk of diabetic nephropathy in type 2 diabetic patients

Abstract Background: As indicated by numerous studies, there exists a relationship between the polymorphism of methylenetetrahydrofolate reductase (MTHFR) and susceptibility to diabetic nephropathy (DN) in various populations; nonetheless, the findings remain inconsistent. Therefore, we carried out a meta-analysis to determine the relationship between the MTHFR gene polymorphism and DN susceptibility. Materials and method: Related studies were identified from PubMed, Cochrane Library, EMBASE, and the China National Knowledge Infrastructure database (time period: from building the library to October 2019). The strength of the association was examined using odds ratios ( ORs ) with 95% confidence intervals ( 95% CIs ). Results: The findings illustrated that the C677T gene polymorphism was significantly associated with an enhanced susceptibility to DN compared to that with diabetes mellitus in allelic ( OR = 1.64, 95% CI = 1.34–2.00, P < .001), dominant ( OR = 1.85, 95% CI = 1.40–2.46, P < .001), codominant (heterozygote: OR = 1.67, 95% CI = 1.27–2.21, P < .001; homozygote: OR = 2.55, 95% CI = 1.82–3.57, P < .001), and recessive ( OR = 1.89, 95% CI = 1.50–2.38, P < .001) models of the overall population. Moreover, as compared with the healthy controls, a significantly augmented susceptibility to DN was found in all 5 genetic comparison models (allelic: OR = 2.06, 95% CI = 1.58–2.67, P < .001; dominant: OR = 2.52, 95% CI = 1.73–3.69, P < .001; codominant: OR = 3.78, 95% CI = 2.50–5.70, P < .001; recessive: OR = 2.41, 95% CI = 1.96–2.97, P < .001). Furthermore, stratifying data by ethnicity revealed substantially augmented vulnerability to DN in not only Caucasian but also Asian populations. Conclusion: The present study suggests that the C677T polymorphism was associated with an augmented susceptibility to DN.