The Pl(A1/A2) polymorphism of glycoprotein IIIa and cerebrovascular events in hypertension: increased risk of ischemic stroke in high-risk patients.
OBJECTIVE
The platelet GPIIIa plays a pivotal role in platelet aggregation. Previous studies showed an association between the GPIIIa Pl(A1/A2) polymorphism and coronary thrombosis, while there is only contrasting evidence about its role in stroke. We explored the possibility that this polymorphism represents a risk factor for stroke in hypertensive patients.


METHODS
We studied two populations. In loco, we genotyped 140 hypertensive control individuals and 28 hypertensive patients with ischemic stroke. Furthermore, we performed an analysis of previously published data of 451 Sardinian hypertensive patients, already characterized and genotyped.


RESULTS
Association analysis revealed that the Pl(A2) distribution was similar between hypertensive patients with and without stroke, but when considering a more homogeneous population of high-risk hypertensive patients, defined according to ESH/ESC 2003 guidelines, we observed that the frequency of the Pl(A2) allele was higher among stroke versus nonstroke patients (stroke, 46.4%; nonstroke, 22.6%; P = 0.01). The multiple regression analysis taking into account this polymorphism among other factors known to contribute to ischemic stroke confirmed the Pl(A2) allele as an additive risk factor for stroke (B = 0.986, Wald = 4.943, P < 0.03), increasing the risk of stroke by 2.9 (95% confidence interval = 1.23-6.85, P < 0.02). Similar results were obtained in the Sardinian population: in hypertensive patients with three or more risk factors, Pl(A2) increases the risk (odds ratio = 2.8, 95% confidence interval = 1.3-6.0, P < 0.001) and is an additive risk factor for stroke (B = 1.073, Wald = 6.920, P < 0.01).


CONCLUSIONS
Our data suggest that the Pl(A2) polymorphism is a genetic determinant of ischemic stroke in a selected high-risk hypertensive population.
Lanni
Francesca
F
Department of Clinical Medicine, Cardiovascular & Immunological Sciences, Federico II University, Naples, Italy.
Santulli
Gaetano
G
Izzo
Raffaele
R
Rubattu
Speranza
S
Zanda
Bastianina
B
Volpe
Massimo
M
Iaccarino
Guido
G
Trimarco
Bruno
B
D000368:Aged; D001794:Blood Pressure / Q000235:genetics*; D002545:Brain Ischemia / Q000150:complications / Q000235:genetics*; D005260:Female; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000150:complications*; D039661:Integrin beta3 / Q000235:genetics*; D007558:Italy; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide / Q000235:genetics / Q000502:physiology*; D012189:Retrospective Studies; D012307:Risk Factors; D020521:Stroke / Q000097:blood / Q000235:genetics*
D039661:Integrin beta3