Published Online
on April 10, 2003

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

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Submitted on December 6, 2002
Accepted on December 10, 2002

MTHFR Gene Polymorphism as a Risk Factor for Silent Brain Infarcts and White Matter Lesions in the Japanese General Population. The NILS-LSA Study

Katsuhiko Kohara MD^*; Michiko Fujisawa MD; Fujiko Ando MD; Yasuharu Tabara PhD; Naoakira Niino MD; Tetsuro Miki MD; and Hiroshi Shimokata MD

From the Department of Geriatric Medicine, Ehime University School of Medicine (K.K., Y.T., T.M.), and Department of Epidemiology, National Institute for Longevity Sciences (M.F., F.A., N.N., H.S.), Ehime, Japan.

^* To whom correspondence should be addressed. E-mail: koharak{at}m.ehime-u.ac.jp.

Background and Purpose--Silent brain infarcts (SBI) and white matter lesions are relatively common neuroimaging findings, especially in the elderly population. The genetic background for SBI and white matter lesions in a large Japanese general population was investigated.

Methods--Subjects were recruited from participants in the National Institute for Longevity Sciences, Longitudinal Study of Aging. Genotyping of methylenetetrahydrofolate reductase (MTHFR) C677T gene mutation and brain MRI examination were performed in 1721 subjects free of any history of stroke. SBI and white matter lesions were diagnosed from MRI findings.

Results--Of 1721 MRI examinations, SBI was observed in 178 (10.3%). The prevalence of SBI and white matter lesions increased with age. The prevalence of SBI was significantly higher in subjects with the MTHFR TT genotype compared with the TC+CC genotype (14.6% versus 9.5%; 42 of 288 versus 136 of 1433; ²=6.71; P=0.010). The stage of white matter lesions was not significantly different. In subjects 60 years of age (n=849), the prevalence of SBI was significantly higher in TT than TC+CC (27.7% versus 16.6%; 36 of 130 versus 119 of 719; ²=9.16; P=0.002). The prevalence of moderately advanced white matter lesions was also significantly higher in TT than TC+CC (60.7% versus 49.0%; 79 of 130 versus 352 of 719; ²=9.16; P=0.002). After correction for other risk factors, the MTHFR TT genotype was independently associated with SBI (odds ratio [OR], 1.72; 95% CI, 1.10 to 2.68; P=0.018) and moderately advanced white matter lesions (OR, 1.58; 95% CI, 1.07 to 2.33; P=0.02).

Conclusions--These findings indicate that the MTHFR TT genotype is an independent risk factor for SBI and white matter lesions in the general Japanese population, especially in elderly subjects.

Key words: amine oxidoreductases • brain infarction • elderly • polymorphism • white matter

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