The MTHFR C677T polymorphism confers a high risk for stroke in both homozygous and heterozygous T allele carriers with Type 2 diabetes

    loading  Checking for direct PDF access through Ovid

Abstract

Objective

Individuals with Type 2 diabetes are at increased risk of stroke. Plasma homocysteine (tHcy) is an independent risk factor for cardiovascular (CV) disease. The methylene–tetrahydrofolate reductase (MTHFR) gene polymorphism (thermolabile variant C677T) is associated with CV risk, partly as a result of increased Hcy, especially in homozygous subjects.

Aim

To relate the occurrence of the MTHFR polymorphism with stroke prevalence by examining allelic frequency and genotype distribution in 165 subjects with Type 2 diabetes studied for the presence of thermolabile C677T MTHFR mutation.

Results

Mean age was 67.7 years, and tHcy 18.2 μmol/l. T allele frequency was 38.5%. MTHFR genotypes were: normal (CC) 40%; heterozygous (CT) 43%; homozygous (TT) 17%. Serum levels of folic acid and B12 vitamin were within normal limits. Stroke prevalence was 14%. Sixty-four per cent of stroke-free subjects had the normal C allele vs. 46% in stroke subjects. The frequencies of genotypes (CC-CT-TT) were (%): 44-41-15 in stroke-free vs. 17-57-26 in stroke patients. Coronary (CAD) and peripheral artery disease (PAD) were common in all groups, with no differences according to genotypes. Stroke prevalence was markedly higher in genotypes CT and TT (18 and 21%) compared with CC (6%). Mean tHcy levels were higher in TT subjects.

Conclusion

The allelic frequency of C677T MTHFR mutation in Type 2 diabetes subjects with stroke is markedly different from that of subjects without stroke. Genotypic characteristics suggest that C677T MTHFR mutation confers a higher risk for stroke to both homozygous and heterozygous T allele carriers that cannot be ascribed solely to raised tHcy and/or lower folate status in CT subjects, nor to phenotypic expression of conventional risk factors for stroke. The impact of the MTHFR polymorphism on stroke may result from T allele-linked deleterious effects, or C allele-linked protection. Confirmatory studies are warranted, as this cohort was not randomly selected, and a type 1 error cannot be ruled out.

Related Topics

    loading  Loading Related Articles