Glycoprotein Ib-alpha Kozak polymorphism in ischemic stroke

Abstract

Background: Recently, a T/C polymorphism in the Kozak sequence of glycoprotein Ib-alpha (GPIb-alpha) gene at position 25 from the initiator ATG codons, has been identified. The presence of -5C allele increases the surface expression of GPIb-IX-V complex in a gene dosage-dependent manner. It has been suggested that higher receptor levels might increase the adhesiveness of the platelets and confer risk for thrombosis. In this study, we aimed to investigate the association between GPIb-alpha Kozak polymorphism and ischemic stroke. Methods: We prospectively and consecutively recruited 231 patients (118 women and 113 men; mean age: 65 +/- 14.2 years) with first ever ischemic stroke admitted to Istanbul Faculty of Medicine Edip Aktin Stroke Unit between April 2007 and June 2009. Demographic features, risk factors, clinical, and etiological subtypes were analyzed. As the control group, 220 unrelated healthy subjects were included. Results: We found that 156 patients had TT, 70 patients had TC, and 5 patients had CC genotype. At least one copy of C allele carriers were overrepresented in the ischemic stroke group (32.5%) compared with controls (23%) [odds ratio (OR): 0.61; 95% confidence interval (CI): 0.40-0.93; P=0.03]. Among etiologic subtypes, the distribution of C allele carriers was the highest in patients with undetermined etiology (45%) and it was significantly higher than controls (OR: 0.36; 95% CI: 0.20-0.65; P=0.0008). In other subtypes, there was no association with Kozak -5C allele. Conclusion: In conclusion, these encouraging preliminary results show that GPIb-alpha T/C polymorphism might increase the risk of ischemic stroke, especially in those with undetermined etiology.