PMID- 10706928
OWN - NLM
STAT- MEDLINE
DCOM- 20000509
LR  - 20190727
IS  - 0049-3848 (Print)
IS  - 0049-3848 (Linking)
VI  - 98
IP  - 1
DP  - 2000 Apr 1
TI  - Common C677T polymorphism in the methylenetetrahydrofolate reductase gene 
      increases the risk for deep vein thrombosis in patients with predisposition of 
      thrombophilia.
PG  - 1-8
AB  - The alanine/valine (A/V) gene polymorphism of 5, 10-methylenetetrahydrofolate 
      reductase (MTHFR), one of the key enzymes catalyzing remethylation of 
      homocysteine, has been reported and the VV genotype is associated with increased 
      plasma homocysteine levels as a result of the reduced activity and increased 
      thermolability of this enzyme. Although previous studies have suggested that the 
      VV genotype is a risk factor for arterial occlusive disease, whether the VV 
      genotype is a risk factor for venous thrombosis is still controversial. Here we 
      screened 72 Japanese patients with deep venous thrombosis (DVT) and 85 controls 
      for this mutation, and we measured plasma levels of homocysteine to determine 
      whether the thermolabile variant with the VV genotype is a risk factor for DVT in 
      a Japanese population. Of the 72 patients with DVT, 10 (13.9%) were found to be 
      homozygous for the VV genotype, and in 6 (7.0%) of 85, control individuals and 
      the difference was not significant (odds ratio=2.12, 95% CI=0.73-6.16, p=0.19). 
      When we divided the DVT patients into subgroups, with and without predisposition 
      of thrombophilia, including deficiencies of proteins C and S, plasminogen, and 
      lupus anticoagulant, the prevalence of the VV genotype in DVT patients with 
      predisposition was significantly higher than that of the normal controls (odds 
      ratio=5.99, 95% CI=1. 56-22.96, p=0.01). However, the prevalence of the VV 
      genotype in DVT patients without predisposition was not significantly different 
      from that of the normal controls (odds ratio=1.20, 95% CI=0.32-4.47, p=0. 75). 
      The plasma homocysteine levels in patients with DVT (11.6+/-5.2 nmol/ml) was not 
      significantly different from that of the control subjects (11.6+/-3.7 nmol/ml). 
      Individuals with the VV genotype showed higher plasma homocysteine levels 
      (15.4+/-6.9 nmol/ml) than did individuals with the AV genotype (11.2+/-3.7 
      nmol/ml, p=0.009) or in individuals with the AA genotype (11.1+/-4.2 nmol/ml, 
      p=0.004). Serum folate and vitamin B12 levels were not correlated with the plasma 
      homocysteine levels. In conclusion, even though homozygosity for the VV genotype 
      of the MTHFR gene was associated with higher plasma homocysteine levels, we found 
      no association between plasma levels of homocysteine and DVT or between the 
      genotype of the MTHFR gene and the DVT incidence. However, we found that the VV 
      genotype of the MTHFR gene is a risk factor for DVT only when combined with the 
      predisposition of thrombophilia.
FAU - Fujimura, H
AU  - Fujimura H
AD  - Department of Surgery II, Osaka University Medical School, Suita, Japan.
FAU - Kawasaki, T
AU  - Kawasaki T
FAU - Sakata, T
AU  - Sakata T
FAU - Ariyoshi, H
AU  - Ariyoshi H
FAU - Kato, H
AU  - Kato H
FAU - Monden, M
AU  - Monden M
FAU - Miyata, T
AU  - Miyata T
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Thromb Res
JT  - Thrombosis research
JID - 0326377
RN  - EC 1.5.- (Oxidoreductases Acting on CH-NH Group Donors)
RN  - EC 1.5.1.20 (Methylenetetrahydrofolate Reductase (NADPH2))
SB  - IM
MH  - Adult
MH  - Aged
MH  - Alleles
MH  - Female
MH  - Genetic Predisposition to Disease
MH  - Humans
MH  - Male
MH  - Methylenetetrahydrofolate Reductase (NADPH2)
MH  - Middle Aged
MH  - Oxidoreductases Acting on CH-NH Group Donors/*genetics
MH  - *Polymorphism, Genetic
MH  - Risk
MH  - Thrombophilia/complications/*genetics
MH  - Thrombophlebitis/etiology/*genetics
EDAT- 2000/03/09 09:00
MHDA- 2000/05/16 09:00
CRDT- 2000/03/09 09:00
PHST- 2000/03/09 09:00 [pubmed]
PHST- 2000/05/16 09:00 [medline]
PHST- 2000/03/09 09:00 [entrez]
AID - S0049-3848(99)00231-5 [pii]
AID - 10.1016/s0049-3848(99)00231-5 [doi]
PST - ppublish
SO  - Thromb Res. 2000 Apr 1;98(1):1-8. doi: 10.1016/s0049-3848(99)00231-5.