title: The roles of methylenetetrahydrofolate reductase 677C>T and 1298A>C polymorphisms in moyamoya disease patients.
abstract: OBJECTIVE
  The methylenetetrahydrofolate reductase (MTHFR) 677C>T and 1298A>C polymorphisms, which are associated with hyperhomocysteinemia and nitric oxide (NO) deficiency (which is related to atherothrombosis and cerebral ischemia), have not been studied in moyamoya disease. A case-control study was performed to investigate whether the MTHFR 677C>T and 1298A>C polymorphisms contribute to moyamoya disease (MMD).
  
  
  METHODS
  One hundred and seven Korean patients with MMD (mean age, 20.85 ± 15.89 years; 66.4 % female) and 232 healthy control subjects (mean age, 23.99 ± 16.16 years; 56.8 % female) were included. Genotyping for the MTHFR 677C>T and 1298A>C polymorphisms and measurements of homocysteine, folate, vitamin B12, and NO in the cerebrospinal fluid (CSF) were performed. The statistical analysis was performed by multivariate linear regression and logistic regression.
  
  
  RESULTS
  The MTHFR 677CT+TT genotype frequency was significantly increased with early-onset MMD (<10 years) compared with late-onset MMD (≥10 years) (adjusted odds ratio, 3.392; 95 % confidence interval, 1.294-8.893, P = 0.013). The MTHFR 677C-1298C/677T-1298A diplotype (1.71 ± 1.23 arbitrary units) presented significantly lower NO levels in the CSF compared with the 677C-1298A/677C-1298A diplotype (11.40 ± 12.24 arbitrary units).
  
  
  CONCLUSIONS
  The MTHFR 677C>T and 1298A>C polymorphisms have restricted roles in the Korean MMD population. Therefore, further studies involving larger and more heterogeneous cohorts are needed to extend our understanding of the influence of polymorphisms in MTHFR and other thrombophilic genes on MMD.
authors.affiliation: Department of Neurosurgery, College of Medicine, Chungbuk National University, Cheongju, South Korea.
authors.forename: Young Seok
authors.initials: YS
authors.lastname: Park
authors.forename: Young Joo
authors.initials: YJ
authors.lastname: Jeon
authors.forename: Hyun Seok
authors.initials: HS
authors.lastname: Kim
authors.forename: In Bo
authors.initials: IB
authors.lastname: Han
authors.forename: Joong-Uhn
authors.initials: JU
authors.lastname: Choi
authors.forename: Dong-Seok
authors.initials: DS
authors.lastname: Kim
authors.forename: Nam Keun
authors.initials: NK
authors.lastname: Kim
mesh_terms: D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005260:Female; D005492:Folic Acid / Q000134:cerebrospinal fluid; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006710:Homocysteine / Q000134:cerebrospinal fluid; D006801:Humans; D016014:Linear Models; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D009072:Moyamoya Disease / Q000134:cerebrospinal fluid / Q000235:genetics*; D009569:Nitric Oxide / Q000134:cerebrospinal fluid; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D056910:Republic of Korea; D014805:Vitamin B 12 / Q000134:cerebrospinal fluid; D055815:Young Adult
chemical_list: D006710:Homocysteine; D009569:Nitric Oxide; D005492:Folic Acid; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D014805:Vitamin B 12
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