Genetic variants of platelet glycoprotein receptors and risk of stroke in young women.
OBJECTIVE
A number of studies have examined the relationship between genetic platelet glycoprotein variants and early-onset atherothrombotic disease, particularly acute myocardial infarction. Data on the association of these genetic susceptibility markers with ischemic stroke are more limited, and their role in hemorrhagic stroke has not been previously examined.


METHODS
We performed genotype analysis for 5 common diallelic platelet glycoprotein polymorphisms in a population-based study of 78 white women aged <45 years with arterial stroke (36 ischemic cases and 42 hemorrhagic cases) and 346 demographically similar control subjects.


RESULTS
The 807T variant of glycoprotein Ia was associated with a 2-fold increased risk of ischemic stroke (age-adjusted odds ratio [OR]=2.24; 95% CI=0.99 to 5.06). The Met(145) allele of glycoprotein Ibalpha was associated with a trend toward an increased risk of ischemic stroke that was more pronounced in the homozygous state (OR=10.36), but the CI is extremely wide because of the small numbers of subjects (95% CI=1.43 to 79.34). Homozygosity for the Ser(843) allele of the glycoprotein IIb was associated with an approximately 5-fold increased risk of ischemic stroke among subgroups of women who carried a diagnosis of hypertension or diabetes (OR=4.51; 95% CI=1.01 to 20.13) or had elevated plasma homocysteine levels (OR=5.94; 95% CI=1.53 to 23.05). The genotype distributions for all 5 platelet glycoprotein polymorphisms were similar among hemorrhagic stroke cases and controls.


CONCLUSIONS
Several inherited platelet glycoprotein variants may be associated with an increased risk of ischemic stroke in young women. These associations seemed to be confined to women with other cardiovascular risk factors. Additional studies involving larger numbers of subjects are needed to confirm these preliminary findings.
Reiner
A P
AP
Departments of Medicine, University of Washington, Seattle, WA 98195-9756, USA. apreiner@u.washington.edu
Kumar
P N
PN
Schwartz
S M
SM
Longstreth
W T
WT
Pearce
R M
RM
Rosendaal
F R
FR
Psaty
B M
BM
Siscovick
D S
DS
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000483:Alleles; D001792:Blood Platelets / Q000737:chemistry; D002545:Brain Ischemia / Q000453:epidemiology / Q000235:genetics; D002543:Cerebral Hemorrhage / Q000453:epidemiology / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D016023:Integrins / Q000235:genetics*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000235:genetics; D019038:Platelet Glycoprotein GPIb-IX Complex; D010980:Platelet Membrane Glycoproteins; D011110:Polymorphism, Genetic; D011956:Receptors, Cell Surface / Q000235:genetics*; D038981:Receptors, Collagen; D012307:Risk Factors; D020521:Stroke / Q000453:epidemiology* / Q000235:genetics*
D016023:Integrins; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D019038:Platelet Glycoprotein GPIb-IX Complex; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D038981:Receptors, Collagen; C032193:glycoprotein receptor GPIb-IX