title: Association of factor V gene polymorphism with arteriovenous graft failure.
abstract: BACKGROUND
  Dialysis grafts fail due to recurrent stenosis and thrombosis. Vasoactive and prothrombotic substances affecting intimal hyperplasia or thrombosis may modify graft outcomes.
  
  
  METHODS
  Genetic polymorphisms association study of patients enrolled in a multicenter randomized clinical trial.
  
  
  METHODS
  354 Dialysis Access Consortium (DAC) Study patients receiving a new graft with DNA samples obtained. Participants were randomly assigned to treatment with aspirin plus dipyridamole versus placebo.
  
  
  METHODS
  DNA sequence polymorphisms for the following candidate genes and their interaction with the study intervention: methylenetetrahydrofolate reductase (MTHFR), heme oxygenase 1 (HO-1), factor V (F5), transforming growth factor β1 (TGFβ1), klotho, nitric oxide synthase (NOS), and angiotensin-converting enzyme (ACE).
  
  
  RESULTS
  Graft failure (>50% stenosis, angioplasty, thrombosis, surgical intervention, or permanent loss of function).
  
  
  RESULTS
  During a median patient follow-up of 34.3 months, 304 grafts failed. After adjusting for clinical factors (patient age, sex, access location, diabetes, cardiovascular disease, baseline aspirin use, body mass index, timing of graft placement, and study treatment) and genetic ancestral background, single-nucleotide polymorphism rs6019 of the factor V gene was associated significantly with graft failure in a dominant model (HR of 1.70 [95% CI, 1.32-2.19; P < 0.001] for G/C and G/G genotypes vs C/C genotypes). There was no significant association between graft failure and polymorphisms of MTHFR, HO-1, TGFβ1, klotho, NOS, or ACE.
  
  
  CONCLUSIONS
  Small sample size.
  
  
  CONCLUSIONS
  The rs6019 genotype of Factor V is associated with increased risk of graft failure. Anticoagulation may reduce graft failure in patients with the G/C or G/G genotypes.
authors.affiliation: Division of Nephrology, University of Alabama at Birmingham, Birmingham, AL, USA. mdallon@uab.edu
authors.forename: Michael
authors.initials: M
authors.lastname: Allon
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.forename: Ivan D
authors.initials: ID
authors.lastname: Maya
authors.forename: Molly S
authors.initials: MS
authors.lastname: Bray
authors.forename: Jose R
authors.initials: JR
authors.lastname: Fernandez
mesh_terms: D000328:Adult; D000368:Aged; D001241:Aspirin / Q000494:pharmacology; D002908:Chronic Disease; D004247:DNA / Q000235:genetics; D004176:Dipyridamole / Q000494:pharmacology; D004311:Double-Blind Method; D005165:Factor V / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000235:genetics*; D006085:Graft Survival / Q000187:drug effects; D006801:Humans; D007674:Kidney Diseases / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D010597:Pharmacogenetics; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D006435:Renal Dialysis; D012189:Retrospective Studies; D058017:Vascular Grafting
chemical_list: D010975:Platelet Aggregation Inhibitors; D004176:Dipyridamole; D005165:Factor V; D004247:DNA; D001241:Aspirin