| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
© 1997 American Heart Association, Inc.
Articles |
Bcl I Polymorphism in the Fibrinogen ß-Chain Gene Is Associated With the Risk of Familial Myocardial Infarction by Increasing Plasma Fibrinogen Levels
A Case-Control Study in a Sample of GISSI-2 Patients
From the Istituto di Ricerche Farmacologiche Mario Negri, Department of Vascular Medicine and Pharmacology, "A. Valenti" Laboratory of Thrombosis Pharmacology, Consorzio Mario Negri Sud, Santa Maria Imbaro, Italy (F.Z., A. Di C., C.A., A.D, M.B.D., L.I.); and Gaubius Laboratory, Leiden, The Netherlands (L.I.).
Correspondence to Licia Iacoviello, MD, Department of Vascular Medicine and Pharmacology, "A. Valenti" Laboratory of Thrombosis Pharmacology, Consorzio Mario Negri Sud, 66030 Santa Maria Imbaro, Italy. E-mail iaco{at}cmns.mnegri.it
Abstract The aim of this study was to investigate the association of the Bcl I ß-chain fibrinogen polymorphism with the risk of acute myocardial infarction (AMI) and its relationship with fibrinogen levels in the Italian population. We studied 102 AMI patients, selected within the framework of the GISSI-2 trial, who had a familial history of arterial thrombosis (at least one first-degree relative suffering from AMI or stroke before 65 years) and 173 control subjects (with neither AMI nor personal or familial history of arterial thrombosis). All subjects were Italian. Patients showed fibrinogen levels higher than control subjects. There was a highly significant difference in allele frequency in cases versus control subjects, the B2 allele frequencies being respectively 0.28 versus 0.17 (P=.002). In multivariate analysis, adjusted for sex, age, smoking habits, and history of hyperlipidemia, hypertension, or diabetes, the (B1B2+B2B2) genotype was associated with a higher risk of AMI (odds ratio 2.4, 95% confidence interval, 1.2 to 4.6). The Bcl I genotype was also associated with fibrinogen levels, independently of gender and smoking habits, the (B1B2+B2B2) subjects showing the highest levels in both cases and control subjects. The difference in fibrinogen levels between cases and control subjects was significantly influenced by the genotype (significant interaction, P=.042) The B2 allele of the Bcl I polymorphism in the ß-chain of the fibrinogen gene is a new factor associated with the risk of familial AMI through its association with fibrinogen levels. These data provide evidence for a causal role of fibrinogen in familial AMI.
Key Words: fibrinogen • polymorphisms • myocardial infarction • family history
This article has been cited by other articles:
 |
|
 |
|
  W. Koch, P. Hoppmann, J. Biele, J. C. Mueller, A. Schomig, and A. Kastrati Fibrinogen Genes and Myocardial Infarction: A Haplotype Analysis Arterioscler. Thromb. Vasc. Biol., April 1, 2008; 28(4): 758 - 763. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Verschuur, M. de Jong, L. Felida, M. P. M. de Maat, and H. L. Vos A Hepatocyte Nuclear Factor-3 Site in the Fibrinogen {beta} Promoter Is Important for Interleukin 6-induced Expression, and Its Activity Is Influenced by the Adjacent -148C/T Polymorphism J. Biol. Chem., April 29, 2005; 280(17): 16763 - 16771. [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]
|
|
|
|
 |
|
 G. H. Gibbons, C. C. Liew, M. O. Goodarzi, J. I. Rotter, W. A. Hsueh, H. M. Siragy, R. Pratt, and V. J. Dzau Genetic Markers: Progress and Potential for Cardiovascular Disease Circulation, June 29, 2004; 109(25_suppl_1): IV-47 - IV-58. [Full Text] [PDF]
|
|
|
|
 |
|
 J. B. Braunstein, D. W. Kershner, P. Bray, G. Gerstenblith, S. P. Schulman, W. S. Post, and R. S. Blumenthal Interaction of Hemostatic Genetics With Hormone Therapy : New Insights To Explain Arterial Thrombosis in Postmenopausal Women Chest, March 1, 2002; 121(3): 906 - 920. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M.A. Laffan Fibrinogen polymorphisms and disease Eur. Heart J., December 2, 2001; 22(24): 2224 - 2226. [PDF]
|
|
|
|
 |
|
 L. Iacoviello, M. Vischetti, F. Zito, and M. Benedetta Donati Genes Encoding Fibrinogen and Cardiovascular Risk Hypertension, November 1, 2001; 38(5): 1199 - 1203. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. S. Williams and P. F. Bray Genetics of Arterial Prothrombotic Risk States Experimental Biology and Medicine, May 1, 2001; 226(5): 409 - 419. [Abstract] [Full Text]
|
|
|
|
 |
|
 T C F Sykes, C Fegan, and D Mosquera Thrombophilia, polymorphisms, and vascular disease Mol. Pathol., December 1, 2000; 53(6): 300 - 306. [Abstract] [Full Text]
|
|
|
|
 |
|
 D. A. Lane and P. J. Grant Role of hemostatic gene polymorphisms in venous and arterial thrombotic disease Blood, March 1, 2000; 95(5): 1517 - 1532. [Full Text] [PDF]
|
|
|
|
|
|
S. O. Brennan, A. P. Fellowes, J. M. Faed, and P. M. George Hypofibrinogenemia in an individual with 2 coding (gamma 82 Aright-arrowG and Bbeta 235 Pright-arrowL) and 2 noncoding mutations Blood, March 1, 2000; 95(5): 1709 - 1713. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. P. Tracy, A. M. Arnold, W. Ettinger, L. Fried, E. Meilahn, and P. Savage The Relationship of Fibrinogen and Factors VII and VIII to Incident Cardiovascular Disease and Death in the Elderly : Results From the Cardiovascular Health Study Arterioscler. Thromb. Vasc. Biol., July 1, 1999; 19(7): 1776 - 1783. [Abstract] [Full Text] [PDF]
|
|