Transforming growth factor β1 genotype polymorphisms determine AV fistula patency in hemodialysis patients

Abstract

Background. In hemodialysis patients with an arteriovenous (AV) fistula, access failure is primarily due to fistula stenosis, which predisposes to thrombosis and subsequent access loss. The risk for access failure differs interindividually, an observation that is independent from vascular anatomy in a significant number of patients. Fistula stenosis is histologically characterized by intimal hyperplasia, which is induced by growth factors, among which transforming growth factor β1 (TGF-β1) is of major importance. The quantitative production of TGF-β1 interindividually differs due to polymorphisms in the gene region encoding the signal sequence of the cytokine. We hypothesized that the TGF-β1 genotype, by influencing the development of arteriovenous fistula stenosis, determines the risk for vascular access failure. Methods. One hundred twenty patients who had undergone placement of an AV fistula for initiation of hemodialysis treatment were genotyped for the polymorphic bases at position +869 and +915 of the TGF-β1 gene. The primary end-point was time from fistula placement to access failure. Results. AV fistula patency was significantly associated with the TGF-β1 genotype (P = 0.0046); patency was 62.4% and 81.2% after 12 months for TGF-β1 high and intermediate producers, respectively. In contrast, AV fistula patency neither differed between diabetic and nondiabetic patients, nor between patients with and without manifest cardiovascular disease. Conclusion. Polymorphisms in the gene region encoding the signal sequence of TGF-β1 influence the risk for hemodialysis access failure. By inducing synthesis of extracellular matrix proteins, overproduction of TGF-β1 may accelerate the development of intimal hyperplasia, resulting in fistula stenosis and subsequent access failure.