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

• Published in: The American journal of cardiology Vol. 89; no. 8; pp. 919 - 923
• Main Authors: Mager, Aviv, Battler, Alexander, Birnbaum, Yochai, Magal, Nurit, Shohat, Mordechai
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 15.04.2002; Elsevier; Elsevier Limited
• Subjects: Adult; Age of Onset; Biological and medical sciences; Cardiology; Cardiology. Vascular system; Cardiovascular disease; Case-Control Studies; Coronary Disease - epidemiology; Coronary Disease - genetics; Coronary heart disease; Female; Heart; Homocysteine - blood; Homozygote; Humans; Hyperhomocysteinemia - epidemiology; Hyperhomocysteinemia - genetics; Male; Medical sciences; Methylenetetrahydrofolate Reductase (NADPH2); Middle Aged; Mutation; Oxidoreductases Acting on CH-NH Group Donors - genetics; Plasma; Risk Factors; Human; Methylenetetrahydrofolate reductase (NADPH); Thiol; Enzyme; Cardiovascular disease; Genotype; Coronary heart disease; Myocardial disease; Genetic determinism; Blood plasma; Vascular disease; Sulfur containing aminoacid; Homocystein; Ischemia; Risk factor; Myocardium; Oxidoreductases; Age
• ISSN: 0002-9149; 1879-1913
• DOI: 10.1016/S0002-9149(02)02239-7

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.