[Gene Polymorphism of 5, 10-methylenetetrahydrofolate reductase as a coronary risk factor].
Hyperhomocysteinemia has been identified as a possible risk factor for coronary artery disease. The association of the alanine/valine (A/V) polymorphism of 5, 10-methylenetetrahydrofolate reductase (MTHFR), one of the key enzymes catalyzing re-methylation of homocysteine, with coronary artery disease was examined in 362 Japanese males with a diagnosis of coronary artery disease confirmed with coronary angiography. The A/V polymorphism was analyzed with PCR followed by Hinf I digestion. The screening of 778 male volunteer controls revealed that the frequency of V allele in Japanese was 0.33, comparable to that in the French Canadian population. The VV genotype, which correlates with increased plasma homocysteine levels due to reduced activity and increased thermolability of this enzyme, was significantly more frequent in patients with coronary artery disease (15.7%, n = 362) than in controls (10.2%, n = 778; p = 0.0067). The association of the VV genotype with coronary artery disease was further increased in patients with > or = 99% stenotic lesion (p = 0.0010). In these patients, 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). The fasting plasma homocysteine levels in VV subjects were higher than those in AV or AA subjects. The VV genotype of MTHFR associated with increased plasma homocysteine levels may represent an important genetic risk factor for coronary artery disease, especially with the occurrence of myocardial infarction.
Morita
H
H
Third Department of Internal Medicine, Faculty of Medicine, University of Tokyo.
Taguchi
J
J
Kurihara
H
H
Kitaoka
M
M
Kaneda
H
H
Kurihara
Y
Y
Maemura
K
K
Shindo
T
T
Minamino
T
T
Ohno
M
M
Yamaoki
K
K
Ogasawara
K
K
Aizawa
T
T
Suzuki
S
S
Yazaki
Y
Y
D000328:Adult; D044466:Asian People; D003327:Coronary Disease / Q000209:etiology*; D006710:Homocysteine / Q000097:blood; D006801:Humans; D007564:Japan; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D008875:Middle Aged; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000235:genetics*; D011110:Polymorphism, Genetic; D012307:Risk Factors
D006710:Homocysteine; D000587:Oxidoreductases Acting on CH-NH Group Donors; D042965:Methylenetetrahydrofolate Reductase (NADPH2)