Gene polymorphism association studies in dialysis:: Vascular access

Complications of the vascular access site for hemodialysis are a major cause of morbidity, suboptimal dialysis, and hospitalization. Vascular access for dialysis that is achieved by central venous catheters is associated with complications such as infection and thrombosis. Arteriovenous fistulas and grafts are also at risk for infectious complications. Further, proliferation of the venous wall with secondary thrombosis is a common pathophysiological process that leads to vascular access dysfunction. Genetic polymorphisms that contribute to vascular access failure are found among factors of the coagulation cascade, and host mediators that induce endothelial dysfunction as well as vessel wall proliferation. The two most common mutations of coagulation factors seem to influence the risk of central venous catheter and fistula thrombosis. Indeed, both the single nucleotide polymorphism of the factor V gene at amino acid position 506 (factor V Leiden mutation) and the prothrombin 20210 polymorphism have been associated with thrombotic complications of the vascular access. Among the endothelium-directed factors, a polymorphism of the methylene tetrahydrofolate reductase gene coding for an enzyme that degrades the endothelium toxic product homocysteine, has been associated with fistula failure. While the angiotensin converting enzyme polymorphism, does not seem to be associated with vascular access complications, polymorphisms of the profibrogenic cytokine transforming growth factor-beta 1 are associated with the prognosis of native arteriovenous fistulae. The role of pro- and anti-inflammatory cytokine gene polymorphisms as prognostic factors for vascular access is yet to be clearly defined.