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J Am Coll Cardiol, 2000; 36:1317-1323 © 2000 by the American College of Cardiology Foundation |
* 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 PlA1/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. PlA1/A2 polymorphism of the gene for GPIIIa has been previously studied in hospital MI patients. Significance of the PlA1/A2 polymorphism in victims of SCD is not known.
METHODS
The PlA1/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 PlA1/A2 polymorphism of GPIIIa is a major risk factor of coronary thrombosis and may be one important predictor of SCD in early middle age.
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