Platelet glycoprotein Ib alpha receptor polymorphisms and recurrent ischaemic events in acute coronary syndrome patients.
OBJECTIVE
To examine the relationship between polymorphisms in the platelet receptor glycoprotein (GP) Ib(alpha) and recurrent ischaemic events, and assess their impact on response to anti-platelet treatment.


RESULTS
1014 patients presenting with unstable coronary syndrome were recruited from the OPUS-TIMI 16 clinical trial of the platelet GPIIb/IIIa antagonist, orbofiban. The subjects were genotyped for two polymorphisms in the gene for GPIb(alpha). These were a T-5C polymorphism in the 5' untranslated Kozak region of the GPIb(alpha) gene, and the variable number of tandem repeats (VNTR) in the macroglycopeptide region.165 patients had events (recurrent ischaemia, urgent revascularisation, myocardial infarction (MI), stroke and death). There was no effect of the number of -5C alleles on composite endpoint frequency among Caucasian subjects (test for trend, p = 0.47). However, MI risk increased with the number of -5C alleles carried, with MI occurring in 2.3% of patients with the -5T/-5T genotype, 5.0% of -5T/-5C, and 16.7% of -5C/-5C (p < 0.01). The effect of treatment on MI outcome was not significantly modified by genotype (test for interaction, p = 0.10). The overall risk of bleeding was not strongly influenced by either the -5C or the VNTR polymorphisms.


CONCLUSIONS
In an unstable coronary syndrome population the T-5C polymorphism in GPIb(alpha) influences risk of subsequent MI.
Kenny
Dermot
D
Department of Clinical Pharmacology, Royal College of Surgeons in Ireland, 123 St. Stephen's Green, Dublin 2, Ireland.
Muckian
Clare
C
Fitzgerald
Desmond J
DJ
Cannon
Christopher P
CP
Shields
Denis C
DC
D000208:Acute Disease; D000368:Aged; D000483:Alleles; D000704:Analysis of Variance; D016001:Confidence Intervals; D003327:Coronary Disease / Q000188:drug therapy / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018598:Minisatellite Repeats / Q000235:genetics; D017202:Myocardial Ischemia / Q000188:drug therapy / Q000235:genetics*; D016017:Odds Ratio; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000037:antagonists & inhibitors / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D011956:Receptors, Cell Surface / Q000235:genetics*; D012307:Risk Factors
D019038:Platelet Glycoprotein GPIb-IX Complex; D011956:Receptors, Cell Surface