The BC genotype of the VNTR polymorphism of platelet glycoprotein Ibalpha is overrepresented in patients with recurrent stroke regardless of aspirin therapy.
BACKGROUND
The contribution of genetic factors to aspirin treatment failure (ATF) for secondary prevention is not settled in patients with ischemic stroke.


METHODS
We assessed the polymorphisms VNTR (A, B, C, D) of glycoprotein (GP) Ibalpha, 807C/T of GP Ia/IIa, and Pl(A1/A2) of GP IIb/IIIa, and the 5-year incidence of major recurrent events in 82 stroke patients with no major sources of cardioembolism (mean age 70, SD 9.0 years; female gender 23%). Using a structured interview, all participants confirmed good compliance with aspirin (100-300 mg/day) for secondary prevention. Demographics and atherothrombotic risk factors assessed included diabetes, hypertension, dyslipemia, smoking, and coronary heart disease.


RESULTS
Thirty-one stroke patients had one recurrent stroke or myocardial infarction within 33 (7-48) months of aspirin onset, while 51 patients demonstrated an uneventful clinical course. Female gender (p < 0.05), diabetes (p < 0.05), dyslipemia (p < 0.05), and the BC genotype of VNTR (25.8 vs. 7.8%, p < 0.05) were more prevalent in patients in whom aspirin failed to prevent clinical events than in those in whom it did not. The BC genotype of VNTR was the only factor that remained associated with ATF in an age-, sex-, and risk factor-adjusted logistic regression analysis (OR 9.6, 95% CI 1.5-61.0).


CONCLUSIONS
The BC genotype of the VNTR polymorphism of GP Ibalpha is an independent predictor of recurrent events in stroke patients treated with aspirin. This finding suggests that high shear-induced platelet activation mediated by GP Ibalpha and von Willebrand factor is an important contributor to ATF in the stroke population.
Cervera
A
A
Stroke Unit, Department of Neurological Sciences, Hospital Clinic, University of Barcelona, and Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain.
Tàssies
D
D
Obach
V
V
Amaro
S
S
Reverter
J C
JC
Chamorro
A
A
D000368:Aged; D001241:Aspirin / Q000627:therapeutic use*; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D015994:Incidence; D038982:Integrin alpha2beta1 / Q000235:genetics; D016015:Logistic Models; D008297:Male; D008562:Membrane Glycoproteins; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D018598:Minisatellite Repeats; D016017:Odds Ratio; D010349:Patient Compliance; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000235:genetics; D019038:Platelet Glycoprotein GPIb-IX Complex; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D055502:Secondary Prevention; D020521:Stroke / Q000188:drug therapy / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D011795:Surveys and Questionnaires; D013997:Time Factors; D017211:Treatment Failure
D038982:Integrin alpha2beta1; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D019038:Platelet Glycoprotein GPIb-IX Complex; C094990:adhesion receptor; D001241:Aspirin