title: MTHFR gene polymorphism as a risk factor for silent brain infarcts and white matter lesions in the Japanese general population: The NILS-LSA Study.
abstract: OBJECTIVE
  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; chi2=6.71; P=0.010). The stage of white matter lesions was not significantly different. In subjects >or=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; chi2=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; chi2=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.
authors.affiliation: Department of Geriatric Medicine, Ehime University, School of Medicine, Onsen-gun, Ehime 791-0295, Japan. koharak@m.ehime-u.ac.jp
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Kohara
authors.forename: Michiko
authors.initials: M
authors.lastname: Fujisawa
authors.forename: Fujiko
authors.initials: F
authors.lastname: Ando
authors.forename: Yasuharu
authors.initials: Y
authors.lastname: Tabara
authors.forename: Naoakira
authors.initials: N
authors.lastname: Niino
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Miki
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Shimokata
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D019943:Amino Acid Substitution; D001921:Brain / Q000473:pathology; D002544:Cerebral Infarction / Q000453:epidemiology / Q000235:genetics*; D003062:Codon / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D018149:Glucose Intolerance / Q000453:epidemiology; D006801:Humans; D020138:Hyperhomocysteinemia / Q000453:epidemiology / Q000235:genetics; D006949:Hyperlipidemias / Q000453:epidemiology; D006973:Hypertension / Q000453:epidemiology; D007564:Japan / Q000453:epidemiology; D008019:Life Style; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D008875:Middle Aged; D020125:Mutation, Missense; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000235:genetics*; D017354:Point Mutation; D020641:Polymorphism, Single Nucleotide; D015995:Prevalence; D012307:Risk Factors; D012907:Smoking / Q000453:epidemiology
chemical_list: D003062:Codon; D000587:Oxidoreductases Acting on CH-NH Group Donors; D042965:Methylenetetrahydrofolate Reductase (NADPH2)