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  • Title: Genetic polymorphism of 5,10-methylenetetrahydrofolate reductase (MTHFR) as a risk factor for coronary artery disease.
    Author: Morita H, Taguchi J, Kurihara H, Kitaoka M, Kaneda H, Kurihara Y, Maemura K, Shindo T, Minamino T, Ohno M, Yamaoki K, Ogasawara K, Aizawa T, Suzuki S, Yazaki Y.
    Journal: Circulation; 1997 Apr 15; 95(8):2032-6. PubMed ID: 9133512.
    Abstract:
    BACKGROUND: Epidemiological studies have identified hyperhomocyst(e)inemia as an independent risk factor for coronary artery disease (CAD). Recently, the alanine/valine (A/V) polymorphism of the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene, one of the key enzymes catalyzing remethylation of homocysteine, has been reported. The VV genotype correlates with increased plasma homocyst(e)ine levels as a result of the reduced activity and increased thermolability of this enzyme. In this study, we examined the distribution of the MTHFR genotypes in Japanese men and the association between the VV genotype and CAD. METHODS AND RESULTS: The diagnoses of CAD of all the studied patients were confirmed by coronary angiography. The MTHFR genotype was analyzed by PCR followed by HinfI digestion. In 778 healthy male subjects, the frequency of the V allele was 0.33, comparable to that in a French Canadian population. In 362 patients with CAD, the VV genotype was significantly more frequent than in control subjects (16% versus 10%, P=.0067). The association of the VV genotype with CAD was further increased in patients with > or = 99% stenotic lesions (18%, P=.0010), whereas no significant association with the VV genotype was observed in patients without a > or = 99% stenosis. When the genotype frequency was compared among patients with different numbers of stenotic coronary arteries, the frequency of the VV genotype was significantly higher in patients with triple-vessel disease (26%) than in patients with single- or double-vessel disease (15% and 14%, respectively). CONCLUSIONS: The VV genotype of MTHFR was also common in the Japanese population and was significantly associated with CAD. The frequency of this genotype in particular was correlated with the severity of disease. The VV genotype associated with a predisposition to increased plasma homocyst(e)ine levels may represent a genetic risk factor for CAD.
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