Glycoprotein IIIA (A1 vs A2)
Glycoprotein IIIa is part of a receptor, the glycoprotein IIb/IIIa receptor, on
the surface of platelets.
This complex binds fibrinogen and von Willibrand factor and it is essential
for platelet aggregation and hemostasis. Two allelic polymorphisms, the
P1A1 and the P1A2 polymorphisms (C to T substitution at base 196 of the
mRNA in exon 2) have been described. The P1A2 is associated with
premature (<55y of age) myocardial infarction, unstable angina and
re-occlusion after PCTR. In addition, the P1A2 allele is associated with
coronary stent thrombosis, adds ratio, 5.26.
The use of stents in occlusive coronary vascular disease has increased
dramatically in the past 3 years. Anti platelet therapy with glycoprotein
IIb/IIIa inhibitors may be useful in preventing stent re-stenosis and stent
thrombosis. although care must be taken that bleeding complications are
avoided. Currently, only intravenous inhibitors are available; oral
inhibitors are in phase II-III trials in humans.
The genotype frequencies for this polymorphism are: P1A1/P1A1, 64%;
P1A1/P1A2, 34%; and P1A2/P1A2, 2.4%.
References:
1. Zotz, RB, et al., (1998) Polymorphism of platelet membrane glycoprotein IIIa;
Human platelet antigen 1b (HPA-1b/P1A2) is an inherited risk factor for premature
myocardial infarction in coronary artery disease. Throm Haemost. 79:731-5.
2. Weiss, EJ, et al., (1996) The platelet glycoprotein IIIa polymorphism P1A2 : an
inherited platelet risk factor for coronary thrombotic events. N. Engl. J.. Med.
334:1090-4.
3. PRISM Study Group; > 30 contributors from several different countries. (1998) A
comparison of Asprin plus Tirofiban with Asprin plus heparin for unstable angina. N.
Engl. J. Med. 338:1498-1505.
4. Ibid. (1998) Inhibition of the platelet glycoprotein IIb/IIIa receptor with Tirofiban in
unstable angina and non-Q-wave myocardial infarction. N. Engl. J. Med. 338:1488
5. Glueck, C.J. M.J. Kupferminc, R.N. Fontaine, P. Wang, B.B. Weksler and A. Eldor.
(2001) Genetic hypofibrinolysis in complicated pregnancies. Obstet. and Gynecol.
97:44-8.
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