Genetic Variation Of Platelet Glycoprotein VI And The Risk Of Venous Thromboembolism

Abstract

Family studies have indicated that heritability explains 50-60% of the venous thromboembolism (VTE) events, and in recent years, several single nucleotide polymorphisms (SNPs) have been found to influence the VTE risk. Glycoprotein 6 (GP6) rs1613662, also known as T13254C, is an A/G single nucleotide variation in amino acid 219, which results in a serine to proline substitution affecting the glycoprotein VI (GPVI) receptor for collagen. Platelets carrying the minor allele (G-allele/Pro219) at GP6 rs1613662 express fewer GPVI receptors, which leads to attenuated platelet adhesion and activation. Previous observational studies in selected populations have consistently demonstrated that carriers of the A-allele at GP6 have a 15% higher risk of VTE than non-carriers, and inversely, that G-allele carriers have a 20% lower VTE risk.