Abstract
Background: The purpose of the present study was to investigate the possible contribution of plasma homocysteine to asymptomatic cerebral infarction (CI) or leukoaraiosis.Methods: The relationship between plasma homocysteine concentrations and cerebral lesions was investigated in 233 elderly diabetic patients (mean age: 74 years) who were divided into three groups based on the neurological and brain MR findings: asymptomatic cerebral infarction (CI), symptomatic CI, and a control group with no evidence of cerebrovascular disease. Plasma total homocysteine concentrations were measured by high‐performance liquid chromatography. The C677T polymorphism in the methylene tetrahydrofolate reductase (MTHFR) gene was assessed by PCR‐RFLP. The total score of T2 high‐intensity lesions on the brain MR images was summed from the focal T2 high‐intensity scores in 24 areas of the brain.Results: Diabetic patients with asymptomatic or symptomatic CI had significantly higher homocysteine concentrations in plasma than the control group. The plasma homocysteine concentration was more strongly associated with the presence and number of small infarctions or infarction of the putamen, which may explain the association between increased plasma homocysteine concentrations and asymptomatic CI in elderly diabetic patients. In the diabetic patients, high plasma homocysteine concentrations were also significantly associated with high scores of total T2 high‐intensity lesions or focal T2 high‐intensity scores in some periventricular regions. Although there was no significant relationship between the MTHFR TT genotype and CI, a significant association was found between the MTHFR TT genotype and total T2 high‐intensity scores.Conclusion: An elevated plasma homocysteine concentration is independently associated with asymptomatic CI and T2 high‐intensity lesions on brain MR images in elderly patients with diabetes mellitus. The association between the MTHFR TT genotype and periventricular T2 high‐intensity lesions, but not with CI, suggests an important effect of C677T MTHFR gene mutation on leukoaraiosis, independent of hyperhomocysteinemia in elderly diabetic patients.
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