Plasma homocysteine, methylenetetrahydrofolate reductase genotypes, and age at onset of symptoms of myocardial ischemia

Aviv Mager, Alexander Battler, Yochai Birnbaum, Nurit Magal, Mordechai Shohat

Research output: Contribution to journalArticlepeer-review

Abstract

Elevated fasting plasma homocysteine is a graded risk factor of coronary artery disease (CAD) and may accelerate onset of CAD. Homozygosity for the C677T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene is commonly but inconsistently associated with hyperhomocysteinemia. In the present study we examined the possible relation between levels of fasting plasma homocysteine and age at CAD onset in different MTHFR genotypes. We studied 182 patients with CAD, 74 patients with early onset CAD (aged ≤45 years), and 108 patients with later onset CAD (aged 46 to 65 years). Plasma homocysteine levels in 90 subjects without CAD were used for control. Fasting plasma homocysteine levels in T/T homozygotes with early onset CAD (20.2 ±12.5 μmol/L) was markedly higher than in T/T homozygotes with later onset CAD (13.4 ± 6.8 μmol/L) and in patients with early onset CAD who were not T/T homozygotes (11.9 ± 3.7 μmol/L; p = 0.034 and p = 0.0001, respectively). CAD developed earlier in T/T homozygotes who were hyperhomocysteinemic (>15 μmol/L) than in the T/T homozygotes who were not (p = 0.036). Plasma homocysteine levels had no effect on age at onset of CAD in patients who were non-T/T genotypes. Homocysteine levels in control subjects and in patients who were non-T/T genotypes were comparable and were not influenced by age. The results reveal an inverse relation between the level of fasting plasma homocysteine and age at onset of CAD in T/T homozygotes as opposed to no association in patients who were non-T/T genotypes. Additionally, these results show that hyperhomocysteinemia and the T/T genotype have a stronger effect on the pathogenesis of CAD when they are combined, and that a marked increase (>15 μmol/L) in fasting plasma homocysteine in T/T homozygotes is a risk factor for early onset of CAD.

Original languageEnglish
Pages (from-to)919-923
Number of pages5
JournalAmerican Journal of Cardiology
Volume89
Issue number8
DOIs
StatePublished - 15 Apr 2002

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