Association of specific haplotypes of GAS6 gene with stroke

Xavier Muñoz; Víctor Obach; Begoña Hurtado; Pablo García de Frutos; Ángel Chamorro; Núria Sala

doi:10.1160/TH06-12-0681

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2007; 98(02): 406-412
DOI: 10.1160/TH06-12-0681

Cardiovascular Biology and Cell Signalling

Schattauer GmbH

Association of specific haplotypes of GAS6 gene with stroke

Xavier Muñoz^*

¹Centre de Genètica Mèdica i Molecular, Institut de Recerca Oncològica-IDIBELL, L’Hospitalet de Llobregat, Spain

,

Víctor Obach

²Stroke Unit, Neurology Service and Institut d’Investigació Biomèdica August Pi i Sunyer (IDIBAPS), Hospital Clínic, Barcelona, Spain

,

Begoña Hurtado^*

¹Centre de Genètica Mèdica i Molecular, Institut de Recerca Oncològica-IDIBELL, L’Hospitalet de Llobregat, Spain

,

Pablo García de Frutos

³Institute for Biomedical Research of Barcelona, IIBB-CSIC-IDIBAPS, Barcelona, Spain

,

Ángel Chamorro

²Stroke Unit, Neurology Service and Institut d’Investigació Biomèdica August Pi i Sunyer (IDIBAPS), Hospital Clínic, Barcelona, Spain

,

Núria Sala^*

¹Centre de Genètica Mèdica i Molecular, Institut de Recerca Oncològica-IDIBELL, L’Hospitalet de Llobregat, Spain

› Author Affiliations

Abstract

Summary

The product of the growth arrest-specific gene 6 (GAS6),a ligand for tyrosine kinase receptors, is a vitamin K-dependent protein, structurally related to anticoagulant protein S. Gas6-deficient mice are protected against thrombosis, demonstrating the importance of this protein in the cardiovascular system. In a preliminary study on GAS6 polymorphisms and atherothrombotic disease we found an association between the AA genotype of the c.834+7G>A GAS6 polymorphism and stroke. In order to further explore this association by considering GAS6 haplotypes and the main stroke subtypes,457 patients with ischemic stroke, 199 with hemorrhagic stroke and 150 asymptomatic controls were genotyped for eight GAS6 polymorphisms and other genetic markers in the same genome region. Association was measured by logistic regression analysis.The THESIAS program was used to measure linkage disequilibrium and haplotype frequencies. In univariate analysis, the GAS6 c.834+7AA 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 subtypes affecting the microvasculature such as lacunar stroke and deep haemorrhage, were grouped together (OR: 0.44; 95%CI: 0.21–0.90). Furthermore, haplotype analysis revealed that association was even stronger when the c.834+7A allele was present in a specific haplotype (CACA) of four GAS6 polymorphisms. From these results we conclude that the A allele of the GAS6 c.834+7G>A polymorphism and more specifically, the CACA haplotype, is less prevalent in patients with stroke, suggesting a protective role for stroke of this haplotype.

Keywords

GAS6 - haplotypes - polymorphisms - stroke

Full Text

References

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