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Blood, 1 January 2008, Vol. 111, No. 1, pp. 183-189. Prepublished online as a Blood First Edition Paper on September 12, 2007; DOI 10.1182/blood-2007-03-078543. This Article Full Text (PDF) Supplemental Figure All Versions of this Article: blood-2007-03-078543v1 111/1/183    most recent Alert me when this article is cited Alert me if a correction is posted 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 HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Boffa, M. B Articles by Koschinsky, M. L Search for Related Content PubMed PubMed Citation Articles by Boffa, M. B Articles by Koschinsky, M. L Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted March 8, 2007 Accepted August 24, 2007 Effect of single nucleotide polymorphisms on expression of the gene encoding thrombin activatable fibrinolysis inhibitor: a functional analysis Michael B Boffa*, Deborah Maret, Jeffrey D Hamill, Nazareth Bastajian, Paul Crainich, Nancy S Jenny, Zhonghua Tang, Elizabeth M Macy, Russell P Tracy, Rendrik F Franco, Michael E Nesheim, and Marlys L Koschinsky Department of Biochemistry, Queen's University, Kingston, Ontario, Canada Department of Pathology, College of Medicine, University of Vermont, Colchester, VT, United States Department of Biochemistry, College of Medicine, University of Vermont, Colchester, VT, United States Fleury Research Institute, Sao Paolo, Brazil Department of Medicine, Queen's University, Kingston, Ontario, Canada * Corresponding author; email: boffam{at}post.queensu.ca. Thrombin-activable fibrinolysis inhibitor (TAFI) is a plasma zymogen that acts as a molecular link between coagulation and fibrinolysis. Numerous single nucleotide polymorphisms (SNPs) have been identified in CPB2, the gene encoding TAFI, and are located in the 5'-flanking region, in the coding sequences, and in the 3'-untranslated region (UTR) of the CPB2 mRNA transcript. Associations between CPB2 SNPs and variation in plasma TAFI antigen concentrations have been described but the identity of SNPs that are causally linked to this variation is not known. In the current study, we investigated the effect of the SNPs in the 5'-flanking region on CPB2 promoter activity and SNPs in the 3'-UTR on CPB2 mRNA stability. Whereas the 5'-flanking region SNPs (with 2 exceptions) did not have a significant effect on promoter activity, either alone or in haplotypic combinations seen in the human population, all of the 3'-UTR SNPs substantially affected mRNA stability. We speculate that these SNPs, in part, contribute to variation in plasma TAFI concentrations via modulation of CPB2 gene expression through an effect on mRNA stability. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: R. Zhang and B. Su MicroRNA regulation and the variability of human cortical gene expression Nucleic Acids Res., July 10, 2008; (2008) gkn431v1. [Abstract] [Full Text] [PDF]

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