PMID- 9133512
OWN - NLM
STAT- MEDLINE
DCOM- 19970516
LR  - 20221207
IS  - 0009-7322 (Print)
IS  - 0009-7322 (Linking)
VI  - 95
IP  - 8
DP  - 1997 Apr 15
TI  - Genetic polymorphism of 5,10-methylenetetrahydrofolate reductase (MTHFR) as a 
      risk factor for coronary artery disease.
PG  - 2032-6
AB  - 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.
FAU - Morita, H
AU  - Morita H
AD  - Third Department of Internal Medicine, Faculty of Medicine, University of Tokyo, 
      Bunkyo-ku, Japan.
FAU - Taguchi, J
AU  - Taguchi J
FAU - Kurihara, H
AU  - Kurihara H
FAU - Kitaoka, M
AU  - Kitaoka M
FAU - Kaneda, H
AU  - Kaneda H
FAU - Kurihara, Y
AU  - Kurihara Y
FAU - Maemura, K
AU  - Maemura K
FAU - Shindo, T
AU  - Shindo T
FAU - Minamino, T
AU  - Minamino T
FAU - Ohno, M
AU  - Ohno M
FAU - Yamaoki, K
AU  - Yamaoki K
FAU - Ogasawara, K
AU  - Ogasawara K
FAU - Aizawa, T
AU  - Aizawa T
FAU - Suzuki, S
AU  - Suzuki S
FAU - Yazaki, Y
AU  - Yazaki Y
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Circulation
JT  - Circulation
JID - 0147763
RN  - 0LVT1QZ0BA (Homocysteine)
RN  - EC 1.- (Oxidoreductases)
RN  - EC 1.5.1.20 (5,10-Methylenetetrahydrofolate Reductase (FADH2))
RN  - EC 1.5.1.20 (Methylenetetrahydrofolate Reductase (NADPH2))
SB  - IM
MH  - 5,10-Methylenetetrahydrofolate Reductase (FADH2)
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Alleles
MH  - Asian People/genetics
MH  - Canada/epidemiology
MH  - Comorbidity
MH  - Coronary Disease/blood/enzymology/*epidemiology
MH  - Disease Susceptibility
MH  - Gene Frequency
MH  - Genotype
MH  - Homocysteine/blood
MH  - Humans
MH  - Japan/epidemiology
MH  - Male
MH  - Methylenetetrahydrofolate Reductase (NADPH2)
MH  - Middle Aged
MH  - Oxidoreductases/*genetics
MH  - Point Mutation
MH  - *Polymorphism, Genetic
MH  - Risk Factors
MH  - White People/genetics
EDAT- 1997/04/15 00:00
MHDA- 1997/04/15 00:01
CRDT- 1997/04/15 00:00
PHST- 1997/04/15 00:00 [pubmed]
PHST- 1997/04/15 00:01 [medline]
PHST- 1997/04/15 00:00 [entrez]
AID - 10.1161/01.cir.95.8.2032 [doi]
PST - ppublish
SO  - Circulation. 1997 Apr 15;95(8):2032-6. doi: 10.1161/01.cir.95.8.2032.