Mikkelsson J, Perola M, Laippala P, Penttilä A, Karhunen P J
Medical School, University of Tampere and Tampere University Hospital, Finland.
J Am Coll Cardiol. 2000 Oct;36(4):1317-23. doi: 10.1016/s0735-1097(00)00871-8.
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.
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.
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.
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.
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.
我们研究了猝死尸检受害者中Pl(A1/A2)多态性与冠状动脉血栓形成、心肌梗死（MI）及心源性猝死（SCD）之间的关联。
心源性猝死是中年早期冠心病的主要症状之一。血小板糖蛋白（GP）IIb/IIIa纤维蛋白原受体在冠状动脉血栓形成和心肌梗死中起关键作用。此前已在医院心肌梗死患者中研究了GPIIIa基因的Pl(A1/A2)多态性。Pl(A1/A2)多态性在SCD受害者中的意义尚不清楚。
在赫尔辛基猝死研究中研究了Pl(A1/A2)多态性，该研究纳入了700名接受尸检的芬兰中年白人男性（33至70岁，平均53岁），他们均死于院外突发或暴力死亡。
该系列中A2等位基因的患病率随年龄下降。这种下降在SCD受害者（n = 281）中观察到，但在暴力死亡男性（n = 258）或死于其他疾病的男性（n = 127）中未观察到。在50岁以下的SCD受害者中，39.7%是A2等位基因携带者，而在50岁以下死于其他原因的男性中这一比例为28.3%（优势比[OR]2.5，p = 0.01）。与无急性冠状动脉血栓形成的SCD男性（n = 242）相比，急性致命性冠状动脉血栓形成的男性（n = 39）更常为A2等位基因携带者（OR 3.4，p < 0.01）（分别为48.7%和24.4%）。此外，有心肌梗死且有近期或陈旧血栓形成的男性（n = 67）比无血栓形成的心肌梗死男性（n = 123）更常为A2等位基因携带者（OR 3.6，p = 0.005）（分别为44.8%和20.3%）。这些关联在60岁以下男性中尤为明显。
我们的结果表明，GPIIIa的Pl(A1/A2)多态性的A2等位基因是冠状动脉血栓形成的主要危险因素，可能是中年早期SCD的一个重要预测指标。
