The methylentetrahydrofolate reductase C677T point mutation is a risk factor for vascular access thrombosis in hemodialysis patients.
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.
Fukasawa
Mizuya
M
Department of Urology and Faculty of Medicine, University of Yamanashi, Japan. mizuya@res.yamanashi-med.ac.jp
Matsushita
Kazumichi
K
Kamiyama
Manabu
M
Mikami
Yuki
Y
Araki
Isao
I
Yamagata
Zentaro
Z
Takeda
Masayuki
M
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
D006710:Homocysteine; D003596:Cytosine; D000587:Oxidoreductases Acting on CH-NH Group Donors; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D013941:Thymine