Published Online
on May 29, 2003

A more recent version of this article appeared on July 1, 2003

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Submitted on December 25, 2002
Accepted on January 23, 2003

Association of Methylenetetrahydrofolate Reductase Gene Polymorphism With Carotid Atherosclerosis Depending on Smoking Status in a Japanese General Population

Nozomu Inamoto MD; Tomohiro Katsuya MD, PhD^*; Yoshihiro Kokubo MD, PhD; Toshifumi Mannami MD, PhD; Takashi Asai MD; Shunroku Baba MD, PhD; Jun Ogata MD, PhD; Hitonobu Tomoike MD, PhD; and Toshio Ogihara MD, PhD

From the Department of Preventive Cardiology, National Cardiovascular Center (N.I., Y.K., T.M., S.B., J.O., H.T.), and Department of Geriatric Medicine, Osaka University Graduate School of Medicine (N.I., T.K., T.A., T.O.),Suita, Osaka, Japan.

^* To whom correspondence should be addressed. E-mail: katsuya{at}geriat.med.osaka-u.ac.jp.

Background and Purpose--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.

Key words: amine oxidoreductases • blood pressure • carotid arteries • Japan • risk factors

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