Circulation, Vol 88, 1463-1469, Copyright © 1993 by American Heart Association
SS Kang, EL Passen, N Ruggie, PW Wong and H Sora
BACKGROUND. To determine whether or not a moderate genetic defect of
homocysteine metabolism is associated with the development of coronary
artery disease, we studied the prevalence of thermolabile
methylenetetrahydrofolate reductase, which is probably the most common
genetic defect of homocysteine metabolism. METHODS AND RESULTS. Three
hundred thirty-nine subjects who underwent coronary angiography were
classified into three groups: (1) patients with severe coronary artery
stenosis (> or = 70% occlusion in one or more coronary arteries or >
or = 50% occlusion in the left main coronary artery), (2) patients with
mild to moderate coronary artery stenosis (< 70% occlusion in one or
more coronary arteries or < 50% occlusion in the left main coronary
artery), and (3) patients with non-coronary heart disease or noncardiac
chest pain (nonstenotic coronary arteries). The thermolability of
methylenetetrahydrofolate reductase was prospectively determined in all
subjects. Plasma homocyst(e)ine levels were then measured in those with
thermolabile methylenetetrahydrofolate reductase. The traditional risk
factors for coronary artery disease were thereafter ascertained by chart
review of all subjects. The prevalence of thermolabile
methylenetetrahydrofolate reductase was 18.1% in group 1, 13.4% in group 2,
and 7.9% in group 3. There was a significant difference between the
prevalence of thermolabile methylenetetrahydrofolate reductase in groups 1
and 3 (P < .04). All individuals with thermolabile
methylenetetrahydrofolate reductase irrespective of their clinical grouping
had higher plasma homocyst(e)ine levels than normal (group 1, 14.86 +/-
5.85; group 2, 15.36 +/- 5.70; group 3, 13.39 +/- 3.80; normal, 8.50 +/-
2.8 nmol/mL). Nonetheless, there was no statistically significant
difference in the plasma homocyst(e)ine concentrations of these patients
with or without coronary artery stenosis. Using discriminant function
analysis, thermolabile methylenetetrahydrofolate reductase was predictive
of angiographically proven coronary artery stenosis. The traditional risk
factors--age, sex, diabetes, smoking, hypercholesterolemia, and
hypertension--were not significantly associated with the presence of
thermolabile methylenetetrahydrofolate reductase. CONCLUSIONS. Thermolabile
methylenetetrahydrofolate reductase is a risk factor for coronary artery
disease and is unrelated to other risk factors.
ARTICLES
Thermolabile defect of methylenetetrahydrofolate reductase in coronary artery disease
Department of Pediatrics, Rush Medical College, Chicago, IL.
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