MTHFR gene polymorphism is susceptible to diabetic retinopathy but not to diabetic nephropathy in Japanese type 2 diabetic patients

Abstract Aims Previously, we have proposed that methylenetetrahydrofolate reductase ( MTHFR ) gene polymorphism (C677T) could be a risk factor for diabetic retinopathy. To support our suggestion, we examined in detail the association of MTHFR polymorphism with diabetic retinopathy and nephropathy in Japanese type 2 diabetic patients. Methods Subjects ( n =190) were free of cardiovascular diseases and were not on hemodialysis. Retinopathy was assessed according to fundamental differentiation; nephropathy was determined according to urinary albumin level; and MTHFR genotype was determined by polymerase chain reaction–restriction fragment length polymorphism. We also analyzed how hyperglycemia affected these three conditions in 131 patients with glycosylated hemoglobin ≥6.5% and fasting blood sugar ≥110 mg/dl. Results The frequency of 677T/677T homozygous subjects with retinopathy was higher than the frequencies of the other two genotypes, and a significant difference was observed in the distribution of the genotypes (677C/677C, 41.9%; 677C/677T, 31.1%; 677T/677T, 61.5%; P Conclusions Our results are highly suggestive of an important role for MTHFR genotype in susceptibility to retinopathy under hyperglycemia, but not to nephropathy. Preventive therapies based on MTHFR polymorphism could delay the onset of retinopathy in type 2 diabetic patients.