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CLINICAL STUDY: ELECTROPHYSIOLOGY

Glycoprotein IIIa Pl^A1/A2 polymorphism and sudden cardiac death

Jussi Mikkelsson, MD^*, Markus Perola, MD, PhD, Pekka Laippala, PhD, Antti Penttilä, MD, PhD and Pekka J. Karhunen, MD, PhD^{* ||}

^* Medical School, University of Tampere and Tampere University Hospital, Tampere, Finland
Department of Human Molecular Genetics, National Public Health Institute, Helsinki, Finland
Biometry Unit, Tampere, School of Public Health, University of Tampere and Tampere University Hospital, Tampere, Finland
Department of Forensic Medicine, University of Helsinki, Helsinki, Finland
^|| Department of Clinical Pathology and Forensic Medicine, University of Kuopio, Kuopio, Finland

Manuscript received December 13, 1999; revised manuscript received March 23, 2000, accepted May 24, 2000.

Reprint requests and correspondence: Dr. Jussi Mikkelsson, Medical School/B-building, University of Tampere, FIN-33014, Tampere, Finland
jm56215{at}uta.fi

OBJECTIVES

We studied the association of the Pl^A1/A2 polymorphism with coronary thrombosis, myocardial infarction (MI) and sudden cardiac death (SCD) in autopsied victims of sudden death.

BACKGROUND

Sudden cardiac death is one of the leading symptoms of coronary heart disease in early middle age. Platelet glycoprotein (GP)IIb/IIIa fibrinogen receptors play a key role in coronary thrombosis and MI. Pl^A1/A2 polymorphism of the gene for GPIIIa has been previously studied in hospital MI patients. Significance of the Pl^A1/A2 polymorphism in victims of SCD is not known.

METHODS

The Pl^A1/A2 polymorphism was studied in the Helsinki Sudden Death Study comprising 700 autopsied middle-aged white Finnish men (33 to 70 years, mean 53 years) who suffered sudden or violent out-of-hospital death.

RESULTS

Prevalence of the A2 allele decreased with age in the series. This decrease was observed among victims of SCD (n = 281) but not in men who died violently (n = 258) or of other diseases (n = 127). Of SCD victims below 50 years, 39.7% were carriers of the A2 allele compared with 28.3% among men under 50 who died of other causes (odds ratio [OR] 2.5, p = 0.01). Men with acute fatal coronary thrombosis (n = 39) were more often (OR 3.4, p < 0.01) carriers of the A2 allele than were men (n = 242) with SCD in the absence of acute coronary thrombosis (48.7% vs. 24.4%, respectively). In addition, men with MI and recent or old thrombosis (n = 67) were more often (OR 3.6, p = 0.005) carriers of the A2 allele than were men (n = 123) with MI in the absence of thrombosis (44.8% vs. 20.3%, respectively). These associations were especially strong in men under 60.

CONCLUSIONS

Our results suggest that the A2 allele of the Pl^A1/A2 polymorphism of GPIIIa is a major risk factor of coronary thrombosis and may be one important predictor of SCD in early middle age.

Abbreviations and Acronyms   AMI = acute myocardial infarction   BMI = body mass index   CHD = coronary heart disease   GPIIIa = glycoprotein IIIa   HSDS = Helsinki Sudden Death Study   MI = myocardial infarction   NBT = nitro-blue-tetrazolium   PHS = Physicians’ Health Study   SCD = sudden cardiac death   vSMC = vascular smooth muscle cells

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