Glycoprotein IIIa PlA polymorphism associates with progression of coronary artery disease and with myocardial infarction in an autopsy series of middle-aged men who died suddenly

被引:66
作者
Mikkelsson, J
Perola, M
Laippala, P
Savolainen, V
Pajarinen, J
Lalu, K
Penttilä, A
Karhunen, PJ
机构
[1] Univ Tampere, Sch Med, FIN-33101 Tampere, Finland
[2] Tampere Univ Hosp, Tampere, Finland
[3] Natl Publ Hlth Inst, Dept Human Mol Genet, Helsinki, Finland
[4] Univ Tampere, Sch Publ Hlth, FIN-33101 Tampere, Finland
[5] Univ Helsinki, Dept Forens Med, FIN-00014 Helsinki, Finland
[6] Univ Kuopio, Dept Clin Pathol & Forens Med, FIN-70211 Kuopio, Finland
关键词
platelet glycoprotein GPIIb/IIIa complex coronary thrombosis; myocardial infarction; polymorphisms; genetics;
D O I
10.1161/01.ATV.19.10.2573
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Glycoprotein IIIa (GPIIIa) has a key role in the aggregation of thrombocytes, and it also mediates intimal hyperplasia after endothelial injuries; the possible association of the Pl(A1/A2) polymorphism of the gene for GPIIIa with coronary thrombosis and with the progression of coronary artery disease (CAD) is still to be confirmed. Therefore, the association of the PIA polymorphism with the development of coronary atherosclerosis, coronary narrowing, and myocardial infarction (MI) was studied in a prospective, consecutive autopsy series of 300 middle-aged, white Finnish men (33 to 69 years) suffering sudden out-of-hospital or violent death. Coronary atherosclerosis was measured morphometrically and the coronary stenosis percentage determined from a cast rubber model of the coronary tree. We found a significant inverse relation (P=0.01) between the Pl(A2)-positive genotype and coronary artery stenosis. The frequency of possessing the Pl(A2) allele was significantly (odds ratio [OR] 0.45, 95% confidence interval [CI] 0.22 to 0.98) lower among men with >50% coronary stenosis (18.3%) than among those with <25% stenosis (32.9%). Although the Pl(A) polymorphism was not directly associated with MI, the Pl(A2) allele was present in 11 of the 22 men (50%) with MI and coronary thrombosis (OR 6.6, 95% CI 2.1 to 22.8) but in only 6 of the 47 (12.8%) with MI associated with severe stenosis in the absence of thrombosis. In Line with this result, men possessing the Pl(A2) allele also had a larger area of fissured and ulcerated complicated lesions in their coronary arteries (P<0.05). The present results suggest that the Pl(A) polymorphism is involved in the development of CAD and MI. Men with the Pl(A2) allele may harbor more thin-walled, vulnerable coronary plaques, plaques prone to rupture, leading to massive, fatal thrombosis. In contrast, men homozygous for the Pl(A1) allele may more often show stable plaques and present with infarction caused by progressive coronary stenosis.
引用
收藏
页码:2573 / 2578
页数:6
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