Methylenetetrahydrofolate reductase gene polymorphism, homocysteine and risk of macroangiopathy in Type 2 diabetes mellitus.

OBJECTIVE

A polymorphism in the gene for methylenetetrahydrofolate reductase (MTHFR) has been reported to be associated with hyperhomocysteinemia and risk for atherosclerotic vascular diseases. In this case-control study, we examined the distribution of the MTHFR genotypes in the Chinese population and clarified the relationship between the gene polymorphism for MTHFR and macroangiopathy in Chinese Type 2 diabetes mellitus.

METHODS

Two hundred and sixteen unrelated patients with Type 2 diabetes mellitus, 112 of whom had macroangiopathy, and 114 healthy control subjects, were recruited. The MTHFR C677T genotype was analyzed by polymerase chain reaction-restriction fragment length polymorphism. Plasma total homocysteine levels were measured using high-performance liquid chromatography (HPLC) with fluorescence detection.

RESULTS

In 114 healthy control subjects, the frequency of the mutant T allele was 31.1%. The genotype distribution did not differ between control subjects and Type 2 diabetic patients (chi2=3.03, p=0.220). Genotypic analysis revealed that the MTHFR genotype was different between diabetic patients with and without macroangiopathy (chi2=12.42, p=0.002). Type 2 diabetic patients with macroangiopathy displayed a greater prevalence of T allele than Type 2 diabetic patients without macroangiopathy (44.6 vs 29.3%; chi2=10.82, p=0.001). The odds ratio for macroangiopathy in Type 2 diabetic patients in presence of T allele was 1.94 [confidence interval (CI) 95%: 1.31-2.89]. Moreover, plasma homocysteine levels were markedly higher in individuals with TT genotype than those with CC or CT genotype.

CONCLUSIONS

The C677T mutation of MTHFR gene is common in the Chinese population. MTHFR C677T gene polymorphism associated with a predisposition to increased plasma homocysteine levels could constitute a useful predictive marker for macroangiopathy in Chinese Type 2 diabetic patients.