RELATION OF A COMMON MUTATION IN METHYLENETETRAHYDROFOLATE REDUCTASE TO PLASMA HOMOCYSTEINE AND EARLY-ONSET CORONARY-ARTERY DISEASE

Objective: In the presence of low serum folate, mutant 5,10-methylenet etrahydrofolate reductase (MTHFR+ [A223V/C677T]) in the homozygous sta te (+/+), may predispose to higher plasma homocysteine (tHct) levels a nd coronary artery disease (CAD). To determine the impact of this rela tionship on predisposition to early-onset GAD, we examined the prevale nce of the mutation and plasma tHct in patients with early-onset GAD a nd compared them to patients manifesting CAD later in life. Methods: T hree hundred patients with history of acute myocardial infarction or a ngina pectoris and angiographically documented CAD were studied. Patie nts consisted of two groups: group 1 (G1 = 150 patients) presenting wi th these findings under age 50; while group 2 (G2 = 150) presented for the first time over age 65 years. Prevalence of the MTHFR+ mutation w as assessed by molecular analysis, and plasma tHct and folate were mea sured. An association of the +/+ genotype with early onset CAD could l ead to its higher prevalence in the younger age group. Results: There was no significant difference in the frequency of the (+/+) genotype b etween the two groups (G1: 11.3% vs. G2: 11.3%). However, patients wit h the (+/+) genotype in both groups had higher tHct when plasma folate was below the mean value (G1: p < 0.0001 while G2: p < 0.01). Conclus ion: The mutant MTHFR genotype was not found to be a determining facto r in early-onset CAD. Higher tHct values were obtained in the older ag e group, which is expected because other studies have shown that tHct levels increase with age. A significant relation was shown between MTH FR genotype and low folate status yielding high tHct levels in those w ith the (+/+) genotype. As this relation was seen in both groups, alth ough to a lesser extent in the older G2, it does not explain the under lying cause of early-onset CAD. Copyright (C) 1998 The Canadian Societ y of Clinical Chemists.