Association of MTHFR C677T and A1298C polymorphisms with the development of type 2 diabetic nephropathy and their interaction with environmental factors

Type 2 diabetic nephropathy is a major cause of end-stage renal disease. MTHFR plays a vital role in folate metabolism, DNA methylation, and RNA synthesis. The aim of this study was to investigate the association between MTHFR C677T and A1298C genomic polymorphisms and development of type 2 diabetic nephropathy in a Chinese population. A hospital-based case-control study was performed. A total of 162 patients with type 2 diabetic nephropathy and 302 controls were recruited from the First Affiliated Hospital of Xinxiang Medical University between January 2013 and February 2015. Genotyping of the MTHFR C677T and A1298C polymorphisms was done by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods. By the chi-square test, a statistically significant difference was observed between the patients and controls in regards to the genetic distributions of MTHFR C677T (χ2=13.51, P=0.001), whereas no significant difference was observed in the genetic distributions of MTHFR A1298C. Individuals carrying with the TT genotype of MTHFR C677T was associated with a significant increase in type 2 diabetic nephropathy risk compared to the CC genotype, and the adjusted OR was 3.79 (1.69-8.70). In addition, the T allele of MTHFR C677T significantly elevated type 2 diabetic nephropathy risk in comparison to the C allele (OR=1.60, OR=1.18-2.17). In conclusion, we found that the MTHFR C677T genomic polymorphism can influence the development of type 2 diabetic nephropathy in a Chinese population.