677C to T mutation in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene and plasma homocyst(e)ine levels in patients with TIA or minor stroke

It was the aim of this study to determine the associations of clinical and laboratory data with plasma homocyst(e)ine levels in patients with transient ischemic attack (TIA) or minor stroke (MS), with special reference to their 677C to T mutation status in the 5,10-methylenetetrahydrofolate reductase (5,10-MTHFR) gene. Seventy-six patients with TIA or MS were investigated at least 3 months after their (last) clinical event. By means of univariate analysis, significant correlations of homocyst(e)ine levels with male gender (P<0.02), age (P<0.0005), creatinine levels (P<0.0002), folate levels (inversely, P<0.05), and alcohol use (P<0.02) were found, but not with vitamin B-12 levels. Multivariate regression analysis, including age, creatinine levels, and folate levels as independent variables, revealed age (P<0.01) and creatinine levels (P<0.02) to be significantly correlated with homocyst(e)ine levels. After adjustment for age, creatinine levels and homocyst(e)ine levels remained significantly correlated to each other (P<0.005), whereas the relation between folate levels and homocyst(e)ine levels was no longer significant (P=0.10). Mutation-positive patients exhibited moderately and statistically non-significantly higher homocyst(e)ine levels than mutation-negative patients, particularly those who were homozygous positive. Homocyst(e)ine levels were closely correlated with creatinine levels (P<0.0002) and with folate levels (inversely, P<0.05), but only in mutation-positive and not in mutation-negative patients. Homozygous positive, heterozygous positive, and mutation-negative patients did not differ with respect to clinical and laboratory data concerning 'risk factors for stroke' or co-existing vascular disease. In conclusion, the associations of creatinine levels and, inversely, of folate levels with plasma homocyst(e)ine levels in patients with TIA or MS are dependent on the 5,10-MTHFR mutation status. Significant correlations between these variables were found only in mutation-positive but not in mutation-negative patients. (C) 1998 Elsevier Science B.V.