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Prepublished online as a Blood First Edition Paper on November 27, 2002; DOI 10.1182/blood-2002-07-2308. This Article Full Text Full Text (PDF) All Versions of this Article: 2002-07-2308v1 102/1/25    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 HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Reiner, A. P. Articles by Psaty, B. M. Search for Related Content PubMed PubMed Citation Articles by Reiner, A. P. Articles by Psaty, B. M. Related Collections Hemostasis, Thrombosis, and Vascular Biology Clinical Trials and Observations Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 July 2003, Vol. 102, No. 1, pp. 25-30 CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS Genetic variants of coagulation factor XIII, postmenopausal estrogen therapy, and risk of nonfatal myocardial infarction Alexander P. Reiner, Susan R. Heckbert, Hans L. Vos, Robert A. S. Ariëns, Rozenn N. Lemaitre, Nicholas L. Smith, Thomas Lumley, Thomas D. Rea, Lucia A. Hindorff, Gina D. Schellenbaum, Frits R. Rosendaal, David S. Siscovick, and Bruce M. Psaty From the Departments of Epidemiology, Medicine, Biostatistics, and Health Services, University of Washington, Seattle, WA; The Hemostasis and Thrombosis Research Center and Department of Clinical Epidemiology, Leiden University Medical Center, the Netherlands; and the Academic Unit of Molecular Vascular Medicine, University of Leeds, United Kingdom. We hypothesized that possession of either of 2 functional coagulation factor XIII polymorphisms, one within subunit A (Val34Leu) and one within subunit B (His95Arg), might modulate the prothrombotic effects of estrogen and help to explain the variation in incidence of arterial thrombotic events among postmenopausal women using hormone replacement therapy. In a population-based case-control study of 955 postmenopausal women, we assessed the associations of factor XIII genotypes and their interactions with estrogen therapy on risk of nonfatal myocardial infarction (MI). The presence of the factor XIIIA Leu34 allele was associated with a reduced risk of MI (odds ratio [OR] = 0.70, 95% confidence interval [95% CI] = 0.51-0.95). The presence of the factor XIIIB Arg95 allele had little association with MI risk. Neither factor XIII polymorphism alone significantly modified the association between the risk of MI and current estrogen use. In exploratory analyses, however, there was a significant factor XIII subunit gene-gene interaction. Compared to women homozygous for both common factor XIII alleles, the Arg95 variant was associated with a reduced risk of MI in the presence of the Leu34 variant (OR = 0.36, 95% CI = 0.17-0.75) but not in the absence of the Leu34 variant (OR = 1.11, 95% CI = 0.69-1.79). Moreover, among women who had at least 2 copies of the variant factor XIII alleles and were current estrogen users, the risk of MI was reduced by 70% relative to estrogen nonusers with fewer than 2 factor XIII variant alleles (P value for interaction = .03). If confirmed, these findings may permit a better assessment of the cardiovascular risks and benefits associated with postmenopausal estrogen therapy. (Blood. 2003;102:25-30) CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: D. M. O. Pruissen, A. J. C. Slooter, F. R. Rosendaal, Y. van der Graaf, and A. Algra Coagulation factor XIII gene variation, oral contraceptives, and risk of ischemic stroke Blood, February 1, 2008; 111(3): 1282 - 1286. [Abstract] [Full Text] [PDF] L. A. Hindorff, B. M. Psaty, C. S. Carlson, S. R. Heckbert, T. Lumley, N. L. Smith, R. N. Lemaitre, M. J. Rieder, D. A. Nickerson, and A. P. Reiner Common Genetic Variation in the Prothrombin Gene, Hormone Therapy, and Incident Nonfatal Myocardial Infarction in Postmenopausal Women Am. J. Epidemiol., April 1, 2006; 163(7): 600 - 607. [Abstract] [Full Text] [PDF] E. M. Scott, R. A.S. Ariens, and P. J. Grant Genetic and Environmental Determinants of Fibrin Structure and Function: Relevance to Clinical Disease Arterioscler. Thromb. Vasc. Biol., September 1, 2004; 24(9): 1558 - 1566. [Abstract] [Full Text] [PDF]

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