Fax +41 61 306 12 34 E-Mail karger@karger.ch www.karger.com Original Paper Cerebrovasc Dis 2008;25:81–86 DOI: 10.1159/000111995 Association of Human Platelet Alloantigen 1 through 5 Polymorphisms with Ischemic Stroke Sarra Saidi a Touhami Mahjoub a Lamia B. Slamia b Sofyan B. Ammou b Abeer M. Al-Subaie c Wassim Y. Almawi c a Research Unit of Hematological and Autoimmune Diseases, Faculty of Pharmacy, University of Monastir, Monastir , and b Department of Neurology, CHU Sahloul, Sousse, Tunisia; c College of Medicine and Medical Sciences, Arabian Gulf University, Manama, Bahrain Introduction Platelets regulate several aspects of primary hemosta- sis by maintaining vascular integrity, wound healing and repair at sites of injury, and by responding to endothelial damage [1]. Altered platelet activation and platelet-de- pendent thromboembolism have been associated with the pathogenesis of cerebrovascular diseases [2], includ- ing stroke [3]. Platelet adhesion and activation are medi- ated by human platelet alloantigens (HPAs), a complex of platelet membrane glycoproteins (Gp) and other cell- bound factors [4, 5]. In excess of 19 HPAs have been iden- tified [6, 7], with HPA-1, -2, -3, -4, and -5 being the most clinically relevant [8]. By altering platelet receptor sensi- tivity, polymorphisms in platelet Gp directly impact platelet susceptibility to activating stimuli, which is linked with an increased risk of atherothrombotic events [9], including acute myocardial infarction [10]. Eleven of the 19 HPAs are on integrin IIb 3 or GP- IIb/IIIa, while of the remaining 8, 3 are on GPIb/IX/V, 2 on integrin 2 1, and 1 each on GPIV, GPV and CD109 [6, 7] . All HPAs identified are biallelic, and map to spe- cific membrane proteins. HPA polymorphisms are due to single base pair substitutions, resulting in single amino acid replacements. HPA-1 (T196C, Leu33Pro), HPA-3 Key Words Human platelet alloantigens  Polymerase chain reaction  Gene polymorphisms  Stroke Abstract Polymorphisms in human platelet alloantigen (HPA)-1 and HPA-3 (GPIIb/IIIa), HPA-2 (GPIb/IX), HPA-4 (GPIIIa) and HPA-5 (GPIa/IIa) were investigated in 216 stroke patients and 318 matched control subjects. HPA genotyping was done by the polymerase chain reaction method using sequence-specific primers. Higher frequencies of the HPA-1 a/b (p ! 0.001) and HPA-5 a/b (p ! 0.001) allele, together with HPA-1 b/b, HPA-5 a/b and HPA-5 b/b genotypes were seen in patients, which was confirmed by regression analysis after controlling for a number of confounding variables. Furthermore, HPA-1 b/b and HPA-5 b/b were significantly associated with the extent of neurological symptoms, and with the recurrence of stroke. Both susceptible (1a/ b-2a/a-3a/b-4a/a-5a/ b) and protective (1a/a-2a/a-3a/a-4a/a-5a/a; 1a/a-2a/a-3a/ b-4a/a-5a/a; 1a/ b- 2a/a-3a/a-4a/a-5a/a; 1a/ b-2a/a-3a/ b-4a/a-5a/a) HPA geno- types were identified. This is the first evidence demonstrat- ing differential association of the common 5 HPA gene variants with stroke, with HPA-1b and HPA-5b representing strong genetic risk factors. Copyright © 2007 S. Karger AG, Basel Received: April 23, 2007 Accepted: July 1, 2007 Published online: December 6, 2007 Wassim Y. Almawi, PhD Department of Medical Biochemistry, College of Medicine and Medical Sciences Arabian Gulf University PO Box 22979, Manama (Bahrain) Tel. +973 3971 7118, Fax +973 1727 1090, E-Mail wassim@agu.edu.bh © 2007 S. Karger AG, Basel 1015–9770/08/0252–0081$24.50/0 Accessible online at: www.karger.com/ced