Mutations in the genes regulating methylene tetrahydrofolate reductase (MTHFR C -> T677) and cystathione beta-synthase (CBS G -> A919, CBS T -> c833)are not associated with myocardial infarction in African Americans

Moderate hyperhomocysteinemia is a putative risk factor for cardiovascular disease. Molecular studies have demonstrated increased plasma homocysteine levels in the presence of DNA mutations in either the methylenetetrahydrofo late reductase (MTHFR) enzyme found in the remethylation pathway or the enz yme cystathione beta -synthase (CBS) of the transsulfuration pathway. To de termine whether the mutation C --> T677 in the MTHFR gene or the T --> C833 / 844ins68 and G --> A919 mutations in the CBS gene are associated with my ocardial infarction (MI) in African Americans, DNA was analyzed from sample s obtained from a case-control study conducted at a large, inner-city hospi tal. One-hundred ten African American subjects with a diagnosis of MI and 1 85 race- and age-matched controls were recruited. Our results demonstrated that 15% of the MI cases were heterozygous for the C --> T677 (MTHFR) mutat ion, while 1.8% were homozygous. When compared to the controls in which 15% were heterozygous and 2.1% were homozygous, no significant association wit h MI was observed. In addition, 34% of the cases were heterozygous for the T --> C833 (CBS) mutation while 6% were homozygous. This is compared to 32% and 5% of the controls having the heterozygous and homozygous genotype, re spectively. No significant association was observed for the T --> C833 (CBS ) mutation among the cases and controls. Although this mutation has no sign ificant association with MI, the prevalence of the heterozygous state was h igher than what has been reported for whites (12%). No mutations for G --> A919 (CBS) were detected in the cases or controls. The racial differences o f the CBS T --> C833 polymorphism suggest that further investigation into t he other areas of the CBS gene is needed. (C) 2001 Elsevier Science Ltd. Al l rights reserved.