PMID- 9743236
OWN - NLM
STAT- MEDLINE
DCOM- 19981001
LR  - 20190831
IS  - 1079-5642 (Print)
IS  - 1079-5642 (Linking)
VI  - 18
IP  - 9
DP  - 1998 Sep
TI  - Methylenetetrahydrofolate reductase gene polymorphism and ischemic stroke in 
      Japanese.
PG  - 1465-9
AB  - Hyperhomocyst(e)inemia has been identified as an independent risk factor for 
      atherosclerotic and thromboembolic diseases such as coronary artery disease, 
      cerebral artery disease, and venous thrombosis. Recently, the alanine/valine 
      (A/V) gene polymorphism of 5,10-methylenetetrahydrofolate reductase (MTHFR), one 
      of the key enzymes that catalyzes the remethylation of homocysteine, was 
      reported. The VV genotype is correlated 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 association between the V allele of the 
      MTHFR gene and ischemic stroke in an elderly Japanese population. The diagnosis 
      of cerebral infarction of all study patients was confirmed by CT of the brain. 
      The MTHFR genotype was analyzed by polymerase chain reaction followed by HinfI 
      digestion. In 256 stroke patients and 325 control subjects, the frequencies of 
      the V allele were 0.45 and 0.32, respectively. The odds ratios and 95% confidence 
      intervals adjusted for the other risk factors were, respectively, 1.51 (1.02 to 
      2.23) for the AV genotype and 3.35 (1.94 to 5.77) for the VV genotype compared 
      with the AA genotype. Both of these effects were statistically significant 
      (P=0.041 and P<0.001, respectively). In patients with multiple infarcts in 
      particular, the allele frequency of the V mutation was 0.56, and the association 
      between the V allele and stroke was highly significant. Plasma homocyst(e)ine 
      levels were significantly higher in patients with the VV genotype than in 
      patients with the AA or AV genotype, especially those with low plasma folate 
      levels. The V allele of the MTHFR gene was significantly associated with cerebral 
      infarction in an elderly Japanese population in a codominant manner. The VV 
      genotype may contribute to risk for ischemic stroke through a predisposition to 
      increased plasma homocyst(e)ine levels, and dietary folate supplementation may be 
      of benefit, particularly to patients with this genotype.
FAU - Morita, H
AU  - Morita H
AD  - Department of Cardiovascular Medicine, Graduate School of Medicine, University of 
      Tokyo, Japan.
FAU - Kurihara, H
AU  - Kurihara H
FAU - Tsubaki, S
AU  - Tsubaki S
FAU - Sugiyama, T
AU  - Sugiyama T
FAU - Hamada, C
AU  - Hamada C
FAU - Kurihara, Y
AU  - Kurihara Y
FAU - Shindo, T
AU  - Shindo T
FAU - Oh-hashi, Y
AU  - Oh-hashi Y
FAU - Kitamura, K
AU  - Kitamura K
FAU - Yazaki, Y
AU  - Yazaki Y
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Arterioscler Thromb Vasc Biol
JT  - Arteriosclerosis, thrombosis, and vascular biology
JID - 9505803
RN  - 0LVT1QZ0BA (Homocysteine)
RN  - EC 1.5.- (Oxidoreductases Acting on CH-NH Group Donors)
RN  - EC 1.5.1.20 (Methylenetetrahydrofolate Reductase (NADPH2))
RN  - EC 3.1.21.4 (Deoxyribonucleases, Type II Site-Specific)
RN  - EC 3.1.21.4 (GANTC-specific type II deoxyribonucleases)
SB  - IM
MH  - Aged
MH  - Alleles
MH  - Brain Ischemia/enzymology/*genetics
MH  - Cerebral Infarction/enzymology/genetics
MH  - Deoxyribonucleases, Type II Site-Specific/metabolism
MH  - Female
MH  - Genotype
MH  - Homocysteine/blood
MH  - Humans
MH  - Japan
MH  - Male
MH  - Methylenetetrahydrofolate Reductase (NADPH2)
MH  - Middle Aged
MH  - Odds Ratio
MH  - Oxidoreductases Acting on CH-NH Group Donors/*genetics
MH  - Polymerase Chain Reaction
MH  - *Polymorphism, Genetic
MH  - Risk Factors
EDAT- 1998/09/22 00:00
MHDA- 1998/09/22 00:01
CRDT- 1998/09/22 00:00
PHST- 1998/09/22 00:00 [pubmed]
PHST- 1998/09/22 00:01 [medline]
PHST- 1998/09/22 00:00 [entrez]
AID - 10.1161/01.atv.18.9.1465 [doi]
PST - ppublish
SO  - Arterioscler Thromb Vasc Biol. 1998 Sep;18(9):1465-9. doi: 
      10.1161/01.atv.18.9.1465.