Am. Carter et al., Association of the platelet glycoprotein IIb HPA-3 polymorphism with survival after acute ischemic stroke, STROKE, 30(12), 1999, pp. 2606-2611
Background and Purpose-The role of polymorphisms of the platelet glycoprote
in (GP) IIb/IIIa receptor in the development of cardiovascular disease has
been the subject of intensive research. The aim of this study was to determ
ine the association of the HPA-3 polymorphism of platelet GPIIb with ischem
ic stroke and subsequent survival and to identify possible interactions of
HPA-3 with classic risk factors.
Methods-HPA-3 genotype was determined by restriction fragment length polymo
rphism in 515 patients with ischemic stroke and 423 healthy, age-matched co
ntrol subjects.
Results-There was no significant difference in the: genotype distribution o
f patients and controls, nor was there any difference when patients were su
bclassified into small- and large-vessel disease. The genotype distribution
of the 231 patients subsequently dying during 2.8 years of follow-up (aa=4
5.0%, ab=46.8 %, bb=8.2%) was significantly different from that of those st
ill alive (aa=37.0%, ab=48.2%, bb=14.8%) (P=0.03). In a Cox regression mode
l, the relative risks for poststroke mortality in patients of aa and nb gen
otype compared with those of bb genotype were 2.42 (95% CI, 1.24 to 4.71) a
nd 2.13 (95% CI, 1.09 to 4.17), respectively, after we accounted for confou
nding factors. In addition. significant interactions of HPA-3 with the PIA
polymorphism of GPIIIa (P=0.002) and with fibrinogen (P=0.01) were identifi
ed in relation to mortality.
Conclusions-HPA-3 is related to poststroke mortality, and the significant i
nteraction of HPA-3 with P1(A) and fibrinogen suggests that it may in some
way influence the interaction of GPIIb/IIIa with fibrinogen, particularly i
n the presence of high fibrinogen.