title: The methylentetrahydrofolate reductase C677T point mutation is a risk factor for vascular access thrombosis in hemodialysis patients.
abstract: BACKGROUND
  Many reports indicate that a high homocysteine (Hcy) level is a potential risk factor for such thrombotic diseases as arteriosclerosis, myocardial infarction, and cerebral infarction in healthy individuals or hemodialysis (HD) patients. The methylentetrahydrofolate reductase (MTHFR) C677T polymorphism has been reported to be closely related to plasma Hcy level.
  
  
  METHODS
  Using a cross-sectional design in this study, the relationship between arteriovenous fistula (AVF) obstruction and the MTHFR C677T point mutation was examined in 337 HD patients.
  
  
  RESULTS
  Results of multivariate analysis showed no significant influence of age, HD therapy duration, sex, or the presence of diabetes mellitus, cerebral infarction, or myocardial infarction. Only the presence of the MTHFR C677T polymorphism yielded a significant difference. Percentages of patients who experienced AVF obstruction were as follows: CC (12.6%), CT (20.3%), and TT (31.8%). The number of those who experienced obstruction was significantly larger with the TT than CC (P < 0.01). Moreover, total obstruction episode ratios were as follows: CC, 1 in 107.21 episodes/patient-month; CT, 1 in 74.08 episodes/patient-month; and TT, 1 in 50.33 episodes/patient-month. Episode percentages tended to be greater when the degree of mutation was greater, and a significant difference was observed between the CC and TT alleles (P < 0.01).
  
  
  CONCLUSIONS
  Although AVF obstruction is affected by numerous factors, there was a strong relationship between MTHFR C677T mutation and AVF obstruction. These findings suggest that the MTHFR C677T point mutation could serve as an important indicator in identifying susceptibility to AVF obstruction.
authors.affiliation: Department of Urology and Faculty of Medicine, University of Yamanashi, Japan. mizuya@res.yamanashi-med.ac.jp
authors.forename: Mizuya
authors.initials: M
authors.lastname: Fukasawa
authors.forename: Kazumichi
authors.initials: K
authors.lastname: Matsushita
authors.forename: Manabu
authors.initials: M
authors.lastname: Kamiyama
authors.forename: Yuki
authors.initials: Y
authors.lastname: Mikami
authors.forename: Isao
authors.initials: I
authors.lastname: Araki
authors.forename: Zentaro
authors.initials: Z
authors.lastname: Yamagata
authors.forename: Masayuki
authors.initials: M
authors.lastname: Takeda
mesh_terms: D001166:Arteriovenous Shunt, Surgical / Q000009:adverse effects*; D003430:Cross-Sectional Studies; D003596:Cytosine; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006710:Homocysteine / Q000097:blood; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood / Q000201:enzymology / Q000235:genetics; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D008875:Middle Aged; D015999:Multivariate Analysis; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000235:genetics*; D017354:Point Mutation / Q000235:genetics*; D006435:Renal Dialysis / Q000009:adverse effects* / Q000379:methods; D012307:Risk Factors; D013927:Thrombosis / Q000097:blood / Q000201:enzymology* / Q000235:genetics*; D013941:Thymine
chemical_list: D006710:Homocysteine; D003596:Cytosine; D000587:Oxidoreductases Acting on CH-NH Group Donors; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D013941:Thymine