HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY The risk of dialysis access thrombosis is related to the transforming growth factor– 1 production haplotype and is modified by polymorphisms in the plasminogen activator inhibitor–type 1 gene

Transforming growth factor– 1 (TGF1) 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 TGF 1 (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 TGF1 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 TGF1 producers was 7.31 (2.15-24.88; P .001). The interaction between low TGF1 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 TGF1 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 TGF1 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. (Blood. 2006;108: 4052-4058)