This Article Full Text Full Text (PDF) 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 Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Mikkelsson, J. Articles by Karhunen, P. J. Search for Related Content PubMed PubMed Citation Articles by Mikkelsson, J. Articles by Karhunen, P. J. Related Collections Clinical genetics Thrombophilia Thrombosis risk factors Acute myocardial infarction Platelets

(Circulation. 2001;104:876.)
© 2001 American Heart Association, Inc.

Clinical Investigation and Reports

Platelet Glycoprotein Ib HPA-2 Met/VNTR B Haplotype as a Genetic Predictor of Myocardial Infarction and Sudden Cardiac Death

Jussi Mikkelsson, MD, PhD; Markus Perola, MD, PhD; Antti Penttilä, MD, PhD; Pekka J. Karhunen, MD, PhD

From the Medical School, University of Tampere and Tampere University Hospital, Tampere (J.M., P.J.K.), and the Department of Forensic Medicine, University of Helsinki, Helsinki (A.P.), Finland; and UCLA Department of Human Genetics, Los Angeles, Calif (M.P.).

Correspondence to Dr Jussi Mikkelsson, University of Tampere, Medical School, B Building, FIN-33014 Tampere, Finland. E-mail jm56215{at}uta.fi

Background—— Sudden cardiac death (SCD) is one of the leading manifestations of coronary heart disease in early middle age. Platelet glycoprotein (GP) Ib-IX-V receptor complexes play a key role in the initial adhesion of platelets to collagen during the formation of a coronary thrombus. The HPA-2 (Thr145 Met) and VNTR polymorphisms of the gene for GP Ib have been studied previously in hospitalized patients with acute coronary syndromes. The significance of these polymorphisms in victims of sudden cardiac death is not known.

Methods and Results—— The association of these 2 polymorphisms with coronary atherosclerosis, coronary artery stenosis, coronary thrombosis, myocardial infarction (MI), and SCD was studied in the Helsinki Sudden Death Study, which comprised 2 large autopsy series, collected 10 years apart during 1981 to 1982 and 1991 to 1992, of 700 middle-aged white Finnish men who suffered sudden or violent out-of-hospital death. The 2 polymorphisms showed an almost complete linkage disequilibrium. Men with acute MI (n=80) and coronary thrombosis (n=65) were more likely to be carriers of the HPA-2 Met allele (OR 2.0 and 2.6, respectively, P<0.005 for both) than were control subjects who died of noncardiac causes (n=367). In men <55 years old, the Met allele was overrepresented (OR 2.2) among victims of SCD (n=98) compared with control subjects (n=249). In men <55 years old, 17 of 29 men with acute MI (58.6%) and 16 of 23 men with coronary thrombosis (69.6%) were carriers of the HPA-2 Met allele compared with the 49 of 249 (19.7%) who had died of noncardiac causes (ORs 5.6 and 9.2, respectively). Similar associations were observed in the separate analyses of both autopsy series.

Conclusions—— Our results suggest that the HPA-2 Met/VNTR B haplotype of the platelet von Willebrand factor and thrombin receptor protein GP Ib-V-IX may be considered to be a major risk factor of coronary thrombosis, fatal MI, and SCD in early middle age.

Key Words: genetics • myocardial infarction • platelets • risk factors • thrombosis

This article has been cited by other articles:

				J. P. Corsetti, D. Ryan, A. J. Moss, D. L. Rainwater, W. Zareba, and C. E. Sparks Glycoprotein Ib{alpha} Polymorphism T145M, Elevated Lipoprotein-Associated Phospholipase A2, and Hypertriglyceridemia Predict Risk for Recurrent Coronary Events in Diabetic Postinfarction Patients Diabetes, May 1, 2007; 56(5): 1429 - 1435. [Abstract] [Full Text] [PDF]

				V. Karhunen, H. Forss, S. Goebeler, H. Huhtala, E. Ilveskoski, O. Kajander, J. Mikkelsson, A. Penttila, M. Perola, H. Ranta, et al. Radiographic Assessment of Dental Health in Middle-aged Men Following Sudden Cardiac Death J. Dent. Res., January 1, 2006; 85(1): 89 - 93. [Abstract] [Full Text] [PDF]

				D. Feinbloom and K. A. Bauer Assessment of Hemostatic Risk Factors in Predicting Arterial Thrombotic Events Arterioscler. Thromb. Vasc. Biol., October 1, 2005; 25(10): 2043 - 2053. [Abstract] [Full Text] [PDF]

				J. Mikkelsson, M. Perola, and P. J. Karhunen Genetics of Platelet Glycoprotein Receptors: Risk of Thrombotic Events and Pharmacogenetic Implications Clinical and Applied Thrombosis/Hemostasis, April 1, 2005; 11(2): 113 - 125. [Abstract] [PDF]

				E. V. Potapov, S. Ignatenko, B. A. Nasseri, M. Loebe, C. Harke, M. Bettmann, A. Doller, V. Regitz-Zagrosek, and R. Hetzer Clinical significance of PlA polymorphism of platelet GP IIb/IIIa receptors during long-term VAD support Ann. Thorac. Surg., March 1, 2004; 77(3): 869 - 874. [Abstract] [Full Text] [PDF]

				A. Snapir, J. Mikkelsson, M. Perola, A. Penttila, M. Scheinin, and P. J. Karhunen Variation in the alpha2B-adrenoceptorgene as a risk factor for prehospitalfatal myocardial infarction and sudden cardiac death J. Am. Coll. Cardiol., January 15, 2003; 41(2): 190 - 194. [Abstract] [Full Text] [PDF]