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


METHODS
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.


RESULTS
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).


CONCLUSIONS
These data suggest that the TNF-alpha -308 A allele is associated with increased PTFE graft thrombosis and failure in hemodialysis patients.
Ram
Sunanda
S
Department of Pediatrics, Louisiana State University Health Sciences Center, 1501 Kings Highway, Shreveport, LA 71130-3932, USA.
Bass
Kristen
K
Abreo
Ken
K
Baier
R John
RJ
Kruger
Thomas E
TE
D001483:Base Sequence; D002408:Catheters, Indwelling / Q000009:adverse effects*; D003430:Cross-Sectional Studies; D004247:DNA / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D007676:Kidney Failure, Chronic / Q000235:genetics / Q000628:therapy; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011138:Polytetrafluoroethylene; D006435:Renal Dialysis / Q000009:adverse effects*; D012189:Retrospective Studies; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D014409:Tumor Necrosis Factor-alpha; D011138:Polytetrafluoroethylene; D004247:DNA