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Blood, 15 December 2006, Vol. 108, No. 13, pp. 4052-4058. Prepublished online as a Blood First Edition Paper on August 24, 2006; DOI 10.1182/blood-2006-06-028902. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2006-06-028902v1 108/13/4052    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Lazo-Langner, A. Articles by Rodger, M. A. Search for Related Content PubMed PubMed Citation Articles by Lazo-Langner, A. Articles by Rodger, M. A. Related Collections Hemostasis, Thrombosis, and Vascular Biology Clinical Trials and Observations Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY 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 From the Division of Hematology and the Division of Nephrology, Department of Medicine, The Ottawa Hospital and University of Ottawa; the Department of Epidemiology and Community Medicine, University of Ottawa; the Clinical Epidemiology Program, Ottawa Health Research Institute; and the Molecular Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario, Ottawa, ON, Canada. 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 TGF1 (869T>C; 915G>C), 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 = .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 = .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 = .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 an additional increase in risk. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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