Association study between polymorphims in GAS6-TAM genes and carotid atherosclerosis.

Abstract

Carotid atherosclerosis (CA) is one of the most common causes of stroke, and recent studies suggest that pathways initiated by the interaction of the plasma vitamin K-dependent protein GAS6 with the tyrosine kinase receptors TYRO3, AXL and MERTK (TAM) may have a relevant role in atherogenesis. Furthermore, our previous studies indicated an association between GAS6 and stroke. The aim of this study was to analyse the genetic association between SNPs and haplotypes in GAS6-TAM genes and CA. We performed a case-control study with 233 CA patients confirmed by nuclear magnetic resonance angiography and 202 patients who suffered from cardioembolic (non atherogenic) stroke. For all included subjects information on established risk factors was available. Genotyping of 16 selected tagSNPs was performed by real-time PCR, using either FRET or TaqMan probes. Adjusted logistic regression (LR) analyses indicated that rs2289743 in TYRO3 and rs869016 in MERTK were associated to CA, decreasing its risk (OR [95%CI]=0.39 [0.16-0.94] and OR [95%CI]=0.31 [0.14-0.69], respectively). Linkage disequilibrium results were consistent with the haplotype blocks described in HapMap and adjusted LR analyses revealed that the haplotype ACAA in MERTK , containing the minor allele of the associated SNP, was also associated to CA. No association was observed with GAS6 and AXL variants, which suggests that CA is not the mechanism underlying the reported association between GAS6 and stroke. The association between TYRO3 and MERTK variants and carotid atherosclerosis found in this study reinforces a physiological role of the GAS6-TAM pathway in atherogenesis.

• Authors: Begoña Hurtado, Nerea Abasolo, Xavier Muñoz, Nadia García, Yolanda Benavente, Francisco Rubio, Pablo García de Frutos, Jerzy Krupinski, Núria Sala
• Journal: Thrombosis and haemostasis (Thromb Haemost) Vol. 104 Issue 3 Pg. 592-8 (Sep 2010) ISSN: 2567-689X [Electronic] Germany
• PMID: 20664904 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Intercellular Signaling Peptides and Proteins
• Proto-Oncogene Proteins
• growth arrest-specific protein 6
• MERTK protein, human
• Receptor Protein-Tyrosine Kinases
• TYRO3 protein, human
• c-Mer Tyrosine Kinase
• Axl Receptor Tyrosine Kinase
• AXL protein, human

Topics

• Aged
• Aged, 80 and over
• Carotid Artery Diseases (genetics, pathology)
• Case-Control Studies
• Chi-Square Distribution
• Female
• Gene Frequency
• Genetic Association Studies
• Genetic Predisposition to Disease
• Haplotypes
• Humans
• Intercellular Signaling Peptides and Proteins (genetics)
• Linkage Disequilibrium
• Logistic Models
• Magnetic Resonance Angiography
• Male
• Middle Aged
• Odds Ratio
• Phenotype
• Polymorphism, Single Nucleotide
• Proto-Oncogene Proteins (genetics)
• Receptor Protein-Tyrosine Kinases (genetics)
• Risk Assessment
• Risk Factors
• Spain
• Stroke (genetics, pathology)
• c-Mer Tyrosine Kinase
• Axl Receptor Tyrosine Kinase