Is C677T polymorphism in methylenetetrahydrofolate reductase gene a risk factor for diabetic nephropathy or diabetes mellitus in a Chinese population?

Background And Aims: To date, case-control studies on the association between C677T polymorphism in methylenetetrahydrofolate reductase (MTHFR) gene and diabetes mellitus (DM) or diabetic nephropathy (DN) in different populations have provided inconclusive results. To clarify the effect of the C677T polymorphism on the risk of both DM and DN in a Chinese population, a meta-analysis was performed.

Methods: A comprehensive literature search was conducted to collect data from all case-control observational studies that investigated association of C677T polymorphism in MTHFR gene with DM or DN in a Chinese population.

Results: Overall, 12 studies in a Chinese population published up to 2011 were combined, and the heterogeneity among them varied from none to moderate. The 677T allele showed significant association with DN (OR = 1.97, 95% CI [1.71, 2.28], p <0.00001), but no relationship with DM (OR = 1.03, 95% CI [0.89, 1.18], p = 0.70) compared with the 677C allele in a Chinese population. Similarly, evidence of significant association with DN was detected in the additive model, the recessive model and the dominant model for allele T (additive model: OR = 3.26, 95% CI [2.46, 4.31], p <0.00001; recessive model: OR = 2.32, 95% CI [1.81, 2.97], p <0.00001; dominant model: OR = 2.35, 95% CI [1.89, 2.91], p <0.00001); however, no relationship with DM was found (additive model: OR = 1.01, 95% CI [0.76, 1.35], p = 0.94; recessive model: OR = 0.98, 95% CI [0.76, 1.26], p = 0.87; dominant model: OR = 1.23, 95% CI [0.91, 1.65], p = 0.18). There were no sources of bias in the selected studies, and the sensitivity analysis (exclusion of studies not in Hardy-Weinberg equilibrium) suggested stability of this meta-analysis.

Conclusions: C677T polymorphism in MTHFR gene may be a risk factor for DN, but not for DM, in a Chinese population.