title: The risk of dialysis access thrombosis is related to the transforming growth factor-beta1 production haplotype and is modified by polymorphisms in the plasminogen activator inhibitor-type 1 gene.
abstract: Transforming growth factor-beta1 (TGF-beta1) and plasminogen activator inhibitor-type 1 (PAI-1) might play a role in the development of fibrosis and stenosis of hemodialysis vascular accesses. We studied polymorphisms in the TGFbeta1 (869T>C; 915G>C), and PAI-1 (4G/5G) genes in 416 hemodialysis patients (107 access thrombosis cases, 309 controls), to determine if they are related to vascular access thrombosis. Three TGF-beta1 production haplotypes (low, intermediate, and high) were defined according to the combination of polymorphisms found. The adjusted odds ratio (OR) and 95% confidence interval (CI) for access thrombosis in low TGF-beta1 producers was 7.31 (2.15-24.88; P = .001). The interaction between low TGF-beta1 production haplotype and the 4G/4G PAI-1 genotype was strongly associated with access thrombosis (adjusted OR 19.3; 95% CI 2.82-132.40; P = .003). Mean access thrombosis-free survival times in years (95% CI) were 14.65 (12.05-17.25), 11.96 (8.67-15.25), and 4.94 (3.06-6.83) in high, intermediate, and low TGF-beta1 producers, respectively (P = .044). Analysis of the synergy index and the case-only cross-product supported the presence of an interaction. We concluded that low TGF-beta1 production haplotype is a risk factor for hemodialysis access thrombosis and that in the presence of the 4G/4G PAI-1 genotype there is an additional increase in risk.
authors.affiliation: Division of Hematology, Department of Medicine, The Ottawa Hospital, University of Ottawa, Ottawa, Ontario Canada.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Lazo-Langner
authors.forename: Greg A
authors.initials: GA
authors.lastname: Knoll
authors.forename: Philip S
authors.initials: PS
authors.lastname: Wells
authors.forename: Nancy
authors.initials: N
authors.lastname: Carson
authors.forename: Marc A
authors.initials: MA
authors.lastname: Rodger
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D018572:Disease-Free Survival; D005260:Female; D005342:Fibrinolysis / Q000235:genetics; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D006435:Renal Dialysis / Q000009:adverse effects; D013927:Thrombosis / Q000209:etiology / Q000235:genetics* / Q000401:mortality; D053773:Transforming Growth Factor beta1 / Q000235:genetics*
chemical_list: D017395:Plasminogen Activator Inhibitor 1; D053773:Transforming Growth Factor beta1