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The graded effect of hyperhomocysteinemia on the severity and extent of coronary atherosclerosis
1Department of Internal Medicine (Cardiology), National Taiwan University Hospital, 7 Chung-Shan South Road, Taipei, Taiwan, ROC.
Insights
Elevated homocysteine (HCY) levels, not MTHFR gene variants, are linked to increased coronary artery disease (CAD) risk and severity in Taiwanese adults. Hyperhomocysteinemia shows a graded effect on CAD, but MTHFR homozygosity is not a significant genetic risk factor.
Area of Science:
- Cardiovascular Genetics
- Nutritional Biochemistry
- Epidemiology
Background:
- Methylenetetrahydrofolate reductase (MTHFR) gene variations and elevated plasma homocysteine (HCY) are implicated in cardiovascular disease.
- The specific impact of MTHFR genotypes and HCY on coronary atherosclerosis severity in Asian populations remains unclear.
Purpose of the Study:
- To investigate the association between MTHFR genotypes, plasma HCY concentrations, and coronary artery disease (CAD) in a Taiwanese population.
- To determine the relationship between these factors and the severity and extent of coronary atherosclerosis.
Main Methods:
- Genotyping for MTHFR polymorphisms and measurement of plasma HCY levels in 192 Taiwanese individuals (116 with CAD, 76 without).
- Statistical analysis to compare genotype frequencies and HCY levels between CAD patients and controls.
- Correlation analysis to assess the relationship between HCY levels and atherosclerosis severity/extent.
Main Results:
- MTHFR genotype distribution was similar between CAD patients and controls; homozygosity was not a significant risk factor.
- CAD patients exhibited significantly higher plasma HCY levels compared to non-CAD subjects.
- Elevated HCY levels correlated positively with multi-vessel disease, severe stenotic lesions (> or = 90%), and showed a graded increase in CAD risk across HCY quartiles.
- HCY concentrations were significantly correlated with both the severity and extent of coronary atherosclerosis.
Conclusions:
- Hyperhomocysteinemia, rather than MTHFR gene homozygosity, is a significant risk factor for CAD and associated atherosclerosis in this Taiwanese population.
- Elevated HCY levels demonstrate a dose-dependent effect on CAD risk and atherosclerosis progression.
- Further research, including vitamin status assessment, is warranted to fully elucidate the MTHFR-CAD relationship.
Abstract:
It is not clear to what extent methylenetetrahydrofolate reductase (MTHFR) gene and hyperhomocysteinemia effect the severity and extent of coronary atherosclerosis in Asian populations. We examined the MTHFR genotypes and plasma homocysteine (HCY) concentrations in 192 Taiwanese and investigated their relationship with coronary artery disease (CAD), and the severity and extent of coronary atherosclerosis. The distribution of MTHFR genotypes was similar in 116 CAD patients and 76 non-CAD subjects. Homozygosity was noted in 8% of CAD patients and 13% of non-CAD subjects (P=0.33; 95% CI, 0. 2-1.6). The geometric mean of HCY values was higher in CAD patients (11.10+/-1.51 micromol/l) than in non-CAD subjects (9.21+/-1.55 micromol/l) (P=0.003). HCY levels were higher in patients with multi-vessel disease (P<0.05) or in patients with > or = 90% stenotic lesions (P=0.005), compared with non-CAD subjects. The CAD risks in the top two HCY quartiles (> or = 14.0 and 10.1-13.9 micromol/l) were 4.0 (95% CI, 1.7-9.2) and 3.2 (95% CI, 1.4-7.4) times higher than in the lowest quartile (< or = 7.9 micromol/l) (P=0.001 and 0.007, respectively). Linear regression analysis showed significant correlations between HCY concentrations and the severity and extent of atherosclerosis (P=0.0001 for both). In conclusion, hyperhomocysteinemia appears to have a graded effect on the risk of CAD as well as the severity and extent of coronary atherosclerosis. Our findings do not support the homozygous genotype of MTHFR as a genetic risk factor for CAD in this Taiwanese population. Perhaps a further study including assessment of vitamin status is needed to better clarify the relationship between MTHFR genotypes and CAD.
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