67ba69a1-4d7e-4a1e-876e-5dda65a7c57b
title
Human vitamin K-dependent  GAS6 : gene structure, allelic variation, and association with stroke.
8ddd21b0-dc1b-4d4e-9abf-5c96196f25b7
abstract
The product of the  growth arrest-specific gene 6  ( GAS6 ), a ligand for the  Axl ,  Sky , and  Mer  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. The present study was aimed at determining the human  GAS6  intron-exon structure and analyzing the gene for the presence of allelic variants that could be associated with atherothrombotic disease. Online analyses allowed us to localize 15  GAS6  exons and to determine the sequence of their intron-flanking regions, in a chromosome 13 region spanning 43.8 kb of DNA. SSCP analysis of PCR-amplified  GAS6  exons with their intron-flanking regions from a minimum of 12 control DNA samples, revealed the presence of eight different variants, which were confirmed to be single nucleotide polymorphisms (SNPs). Three of them ( c.1263G>C ,  c.1332C>T , and  c.1869T>C ) are localized in exons 11, 12, and 14, and appear to be neutral since they do not modify the encoded amino acid. The other SNPs ( c.280+170C>G ,  c.712+26G>A ,  c.713-155C>T ,  c.834+7G>A , and  c.1478-94C>G ) are in introns 3, 7, 8, and 12. A preliminary analysis of five of these SNPs in a group of 110 healthy controls and 188 patients with atherothrombotic disease has revealed statistically significant differences between controls and stroke patients in the allelic distributions of one of these variants ( c.834+7G>A  in intron 8). The SNP identification in  GAS6  reported here would be very useful in future association studies aimed at determining the physiologic role of  GAS6  in stroke and other human diseases.