Association of methylenetetrahydrofolate reductase gene polymorphism with carotid atherosclerosis depending on smoking status in a Japanese general population.
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.
Inamoto
Nozomu
N
Department of Geriatric Medicine, National Cardiovascular Center, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Katsuya
Tomohiro
T
Kokubo
Yoshihiro
Y
Mannami
Toshifumi
T
Asai
Takashi
T
Baba
Shunroku
S
Ogata
Jun
J
Tomoike
Hitonobu
H
Ogihara
Toshio
T
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
D006710:Homocysteine; D000587:Oxidoreductases Acting on CH-NH Group Donors; D042965:Methylenetetrahydrofolate Reductase (NADPH2)