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Thermolabile defect of methylenetetrahydrofolate reductase in coronary artery disease
S S Kang1, E L Passen, N Ruggie
1Department of Pediatrics, Rush Medical College, Chicago, IL.
Insights
A common genetic defect, thermolabile methylenetetrahydrofolate reductase, is linked to coronary artery disease. This finding is independent of traditional risk factors, highlighting a new area for cardiovascular health research.
Area of Science:
- Cardiovascular Genetics
- Metabolic Disorders
- Nutrigenomics
Background:
- Coronary artery disease (CAD) is a leading cause of mortality worldwide.
- Genetic factors play a significant role in CAD development.
- Homocysteine metabolism defects are implicated in cardiovascular risk.
Purpose of the Study:
- To investigate the association between a common genetic defect in homocysteine metabolism and the development of coronary artery disease.
- To determine if thermolabile methylenetetrahydrofolate reductase (tMTHFR) is a risk factor for CAD.
Main Methods:
- A prospective study involving 339 subjects undergoing coronary angiography.
- Classification of subjects into groups based on CAD severity (severe, mild-to-moderate, none).
- Determination of tMTHFR prevalence and measurement of plasma homocyst(e)ine levels.
Main Results:
- The prevalence of tMTHFR was significantly higher in patients with severe CAD (18.1%) compared to those without (7.9%).
- Individuals with tMTHFR had elevated plasma homocyst(e)ine levels, but concentrations did not differ significantly between CAD groups.
- Discriminant function analysis indicated tMTHFR predicts angiographically proven CAD.
Conclusions:
- Thermolabile methylenetetrahydrofolate reductase is identified as an independent risk factor for coronary artery disease.
- The presence of tMTHFR is not associated with traditional CAD risk factors such as age, sex, diabetes, smoking, hypercholesterolemia, or hypertension.
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.