title: Association of methylenetetrahydrofolate reductase gene polymorphism with carotid atherosclerosis depending on smoking status in a Japanese general population.
abstract: OBJECTIVE
  The association of the methylenetetrahydrofolate reductase gene (MTHFR) with carotid atherosclerosis remains inconsistent. This may be due to small sample size and inappropriate analysis. We investigated the association of C677T/MTHFR with blood pressure and carotid atherosclerosis in a Japanese general population.
  
  
  METHODS
  Subjects (30 to 89 years of age; 1693 women, 1554 men) who gave informed consent were randomly selected from a general population in Suita, Japan. MTHFR genotypes were determined by TaqMan polymerase chain reaction. Carotid atherosclerosis was evaluated by high-resolution ultrasonography with atherosclerotic indexes of intimal-medial thickness (IMT), maximum IMT in the common carotid artery (CCA), plaque score, and stenosis (>50%).
  
  
  RESULTS
  Age-adjusted diastolic blood pressure was significantly higher in women with the TT genotype than in those with the CC genotype. In a recessive model (CC+CT versus TT), all adjusted odds ratios for hypertension and >50% stenosis in women were 1.42 and 3.42 (95% confidence intervals, 1.01 to 1.99 and 1.23 to 9.53), respectively. In women, maximum IMT in CCA for smokers with the TT genotype was significantly higher than for smokers with the CC genotype and nonsmokers with the TT genotype (P<0.05).
  
  
  CONCLUSIONS
  Our study suggests that the MTHFR TT genotype is a risk factor for hypertension and carotid stenosis in women. Significant interactions between C677T/MTHFR and smoking on maximum IMT in CCA were observed in women but not in men. Smoking cessation for subjects with the TT genotype is important in the prevention of cerebrovascular disease.
authors.affiliation: Department of Geriatric Medicine, National Cardiovascular Center, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Nozomu
authors.initials: N
authors.lastname: Inamoto
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Katsuya
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Kokubo
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Mannami
authors.forename: Takashi
authors.initials: T
authors.lastname: Asai
authors.forename: Shunroku
authors.initials: S
authors.lastname: Baba
authors.forename: Jun
authors.initials: J
authors.lastname: Ogata
authors.forename: Hitonobu
authors.initials: H
authors.lastname: Tomoike
authors.forename: Toshio
authors.initials: T
authors.lastname: Ogihara
mesh_terms: D000328:Adult; D017677:Age Distribution; D000368:Aged; D000369:Aged, 80 and over; D001794:Blood Pressure / Q000235:genetics; D002339:Carotid Arteries / Q000000981:diagnostic imaging; D002340:Carotid Artery Diseases / Q000000981:diagnostic imaging / Q000201:enzymology* / Q000453:epidemiology / Q000235:genetics*; D015897:Comorbidity; D005260:Female; D005838:Genotype; D006710:Homocysteine / Q000097:blood; D006801:Humans; D006973:Hypertension / Q000453:epidemiology; D007564:Japan / Q000453:epidemiology; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D008875:Middle Aged; D016017:Odds Ratio; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000235:genetics*; D011110:Polymorphism, Genetic; D015995:Prevalence; D012307:Risk Factors; D017678:Sex Distribution; D012737:Sex Factors; D012907:Smoking / Q000453:epidemiology; D014463:Ultrasonography; D014505:Urban Population / Q000706:statistics & numerical data
chemical_list: D006710:Homocysteine; D000587:Oxidoreductases Acting on CH-NH Group Donors; D042965:Methylenetetrahydrofolate Reductase (NADPH2)