| The risk of dialysis access thrombosis is related to the transforming growth factor-beta1 production haplotype and is modified by polymorphisms in the plasminogen activator inhibitor-type 1 gene. | |
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MedLine Citation:
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PMID: 16931622 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Transforming growth factor-beta1 (TGF-beta1) 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 TGFbeta1 (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-beta1 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-beta1 producers was 7.31 (2.15-24.88; P = .001). The interaction between low TGF-beta1 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-beta1 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-beta1 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. |
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Authors:
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Alejandro Lazo-Langner; Greg A Knoll; Philip S Wells; Nancy Carson; Marc A Rodger |
Publication Detail:
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Type: Clinical Trial; Comparative Study; Journal Article; Multicenter Study; Research Support, Non-U.S. Gov't Date: 2006-08-24 |
Journal Detail:
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Title: Blood Volume: 108 ISSN: 0006-4971 ISO Abbreviation: Blood Publication Date: 2006 Dec |
Date Detail:
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Created Date: 2006-12-06 Completed Date: 2007-01-17 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7603509 Medline TA: Blood Country: United States |
Other Details:
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Languages: eng Pagination: 4052-8 Citation Subset: AIM; IM |
Affiliation:
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Division of Hematology, Department of Medicine, The Ottawa Hospital, University of Ottawa, Ottawa, Ontario Canada. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Aged Aged, 80 and over Case-Control Studies Disease-Free Survival Female Fibrinolysis / genetics Follow-Up Studies Genetic Predisposition to Disease* Haplotypes Humans Male Middle Aged Plasminogen Activator Inhibitor 1 / genetics* Polymorphism, Single Nucleotide* Renal Dialysis* / adverse effects Thrombosis / etiology, genetics*, mortality Transforming Growth Factor beta1 / genetics* |
| Chemical | |
Reg. No./Substance:
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0/Plasminogen Activator Inhibitor 1; 0/Transforming Growth Factor beta1 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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