Submitted June 13, 2006
Accepted August 2, 2006
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
Alejandro Lazo-Langner, Greg A Knoll, Philip S Wells, Nancy Carson, and Marc A Rodger*
The Ottawa Hospital and University of Ottawa, Ottawa, Ontario, Canada
Molecular Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario, Ontario, Canada
* Corresponding author; email: mrodger{at}ohri.ca.
Transforming growth factor-
1 (TGF-1) 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 (869 T
C; 915 GC), 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 TGF-1 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 TGF-1 producers was 7.31 (2.15, 24.88; p=0.001). The interaction between low TGF-1 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=0.003). 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 TGF-1 producers, respectively (p=0.044). Analysis of the synergy index and the case-only cross-product supported the presence of an interaction. We concluded that low TGF-1 production haplotype is a risk factor for hemodialysis access thrombosis and that in the presence of the 4G/4G PAI-1 genotype there is a further increase in risk.
