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.
OBJECTIVE: The platelet GPIIIa plays a pivotal role in platelet aggregation. Previous studies showed an association between the GPIIIaPl(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 hypertensivepatients. METHODS: We studied two populations. In loco, we genotyped 140 hypertensive control individuals and 28 hypertensivepatients with ischemic stroke. Furthermore, we performed an analysis of previously published data of 451 Sardinian hypertensivepatients, already characterized and genotyped. RESULTS: Association analysis revealed that the Pl(A2) distribution was similar between hypertensivepatients with and without stroke, but when considering a more homogeneous population of high-risk hypertensivepatients, defined according to ESH/ESC 2003 guidelines, we observed that the frequency of the Pl(A2) allele was higher among stroke versus nonstrokepatients (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 hypertensivepatients 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.
Authors: M Ciccarelli; G Santulli; A Campanile; G Galasso; P Cervèro; G G Altobelli; V Cimini; L Pastore; F Piscione; B Trimarco; G Iaccarino Journal: Br J Pharmacol Date: 2007-12-17 Impact factor: 8.739
Authors: Tiffany L Mathias; Karen C Albright; Amelia K Boehme; Alexander J George; Dominique Monlezun; Erica Jones; T Mark Beasley; Sheryl Martin-Schild Journal: J Cardiovasc Dis Date: 2013-10
Authors: Qi Yuan; Jingyi Yang; Gaetano Santulli; Steven R Reiken; Anetta Wronska; Mindy M Kim; Brent W Osborne; Alain Lacampagne; Yuxin Yin; Andrew R Marks Journal: Proc Natl Acad Sci U S A Date: 2016-07-08 Impact factor: 11.205