Tumor necrosis factor-alpha -308 gene polymorphism is associated with synthetic hemodialysis graft failure.

Progressive venous stenosis mediated, in part, by inflammatory cytokines is a major cause of synthetic hemodialysis graft failure. A tumor necrosis factor-alpha (TNF-alpha) gene polymorphism (G to A, position -308) has been shown to increase plasma cytokine levels and severity of diseases with an underlying inflammatory component. We genotyped 67 patients with synthetic polytetrafluoroethylene (PTFE) grafts and examined the association of the high-(AA or GA) and low- (GG) production TNF-alpha-08 genotypes with the rate of graft failures/thrombosis and graft survival. Hemodialysis patients with the high-production TNF-alpha genotypes had a significantly increased rate of PTFE graft failure at 90 days (37.2% versus 14%) and 1 year (62.8% versus 34.4%) after graft placement compared with patients with the low-production genotype (respectively). Hemodialysis patients with the high-production TNF-alpha genotypes had significantly lower cumulative PTFE graft survival at 1 year (29.4% +/- 11.1% versus 71.2 +/- 6.8%) and 2 years (22.1% +/- 10.5% versus 48.2 +/- 8.1%) compared with patients with the low-production genotype (respectively). Patients with the A allele had approximately twice the mean thrombosis rate compared with those who had the low-production TNF-alpha genotype (3.3 +/- 0.8 versus 1.7 +/- 0.4 thromboses/patient/year, respectively; mean +/- SEM, p < .05). These data suggest that the TNF-alpha -308 A allele is associated with increased PTFE graft thrombosis and failure in hemodialysis patients.