Variability of GP6 gene in patients with sticky platelet syndrome and deep venous thrombosis and/or pulmonary embolism

摘要

The GP6 gene encodes the GPVI, a crucial platelet membrane glycoprotein, for adequate platelet activation, adhesion and aggregation. The objectives of the present study were to assess the genetic variability of the GP6 gene in patients with platelet hyperaggregability phenotype, known as sticky platelet syndrome (SPS) manifesting as deep vein thrombosis (DVT), and/or pulmonary embolism, and in controls; and to evaluate its role in the pathogenesis of venous thromboembolism (VTE) in SPS. Seventy-seven patients with SPS and 77 healthy blood donors as controls were enrolled. Light transmission aggregometry was used to diagnose SPS according to the method of Mammen and Bick. Seven single-nucleotide polymorphisms (SNPs) of the GP6 gene (rs1654410, rs1671153, rs1654419, rs11669150, rs12610286, rs1654431, rs1613662) were assessed using restriction fragment length polymorphism analysis. A significant association between 1613662-G [P<0.05, odds ratio (OR) 2.087, confidence interval (CI) 1.049-4.148], 1654419-A (P<0.05, OR 2.161, CI 1.020-4.577) and VTE was found in patients with SPS. The analysis based on SPS type revealed a significantly higher occurrence of 1671153-G (P<0.05, OR 2.317, CI 1.103-4.865) and 1654419-A (P<0.05, OR 2.317, CI 1.103-4.865) in the SPS type II compared to the control group. No association between the studied GP6 genotypes and the severity of VTE (pulmonary embolism vs. DVT) was found. In the patients, significant positive relationship between the 1671153-G, 1654419-A, 1613662-G alleles and male sex was observed. GP6 SNPs 1613662-G, 1671153-G and 1654419-A alleles are associated with an increased risk of VTE in SPS. They could contribute to the SPS phenotype.