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Title

Association of specific haplotypes of gas6 gene with atherosclerotic stroke

AuthorsObach, Víctor; Muñoz, Xavier; Hurtado Villarejo, Begoña ; García de Frutos, Pablo ; Gómez-Choco, Manuel; Sala, Núria; Chamorro, Ángel
Issue Date2007
AbstractBackground: The product of the growth arrest-specific gene 6 (GAS6)is a vitamin K-dependent protein with anti-apoptotic and pro-thrombotic effects. Its structure is highly homologous with that of anticoagulant protein S. Gas6-deficient mice are protected against thrombosis, demonstrating the importance of this protein in the vascular system. In a preliminary study on GAS6 polymorphisms and atherothrombotic disease we found an association between the AA genotype of the c.8347GA GAS6 polymorphism and stroke. The purpose of this study was to confirm and further analyze these results in a larger and independent stroke population using genotype and haplotype studies. Methods: 656 patients with stroke (457 ischemic and 199 hemorrhagic) and 150 asymptomatic controls were genotyped for eight GAS6 polymorphism (280170 CG, c.71226 GA,c.713–155 TC, c.8347 GA, c.1263 GC, c.1332 CT, c.1478–94 CG, c.1869 TC). Association was measured by logistic regression analysis. The THESIAS program was used to measure linkage disequilibrium and haplotype frequencies. Results: In a univariate analysis the GAS6 c.8347AA genotype was found associated with decreased risk for stroke (OR:0.59;95%CI:0.37– 0.93). After adjustment for vascular risk factors, association was maintained when stroke with macro and microatherosclerosis, such as atherotrombotic and lacunar stroke and deep hemorrhage, were grouped together (OR:0.50;95%CI:0.26–0.96). Furthermore, haplotype analysis revealed that association was even stronger for ischemic stroke (OR:0.48;95%CI:0.28–0.83) when the c.8347 A allele was present in a specific haplotype (CACA) of four GAS6 polymorphisms of the 5’ region (c.280170 CG, c.71226 GA,c.713–155 TC, c.8347 GA). Conclusion: The A allele of the c.8347 GA polymorphism in GAS6 and more strongly the CACA haplotype, are less prevalent in patients with stroke than in controls, suggesting a protective role for stroke of this haplotype.
URIhttp://hdl.handle.net/10261/83378
Appears in Collections:(IIBB) Comunicaciones congresos
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