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The aim of our study was to evaluate GP6 gene in patients with sticky platelet syndrome (SPS) and fetal loss. Platelet aggregability was tested with platelet-rich plasma using PACKS-4 aggregometer (Helena Laboratories). High-resolution melting analysis on LightCycler 480 II (Roche Diagnostics) was used for single-nucleotide polymorphism (SNP) genotyping. We examined 64 patients with SPS and 54 control participants. We found significantly higher occurrence of 5 SNPs in patients with SPS versus controls (rs1671152, rs1654433, rs1613662, rs1654416, and rs2304167). Moreover, the haplotype analysis showed a significantly higher occurrence of 7 haplotypes in patients with SPS compared to controls (acgg and aagg in GP6_5reg haplotype; ccgt in GP6_3reg haplotype; gg and ta in GP6_REG haplotype; SKTH and PEAN in GP6_PEAN haplotype). Our results, especially higher occurrence of 4 nonsynonymous variants within the coding region, support the idea that GP6 polymorphisms are associated with the platelet hyperaggregability accompanied by fetal loss.

Disequilibrium of hemostasis is central to the pathogenesis of all thromboses, and platelets are essential for primary hemostasis. The platelet membrane glycoprotein receptor is involved in the clot formation in blood; therefore, the changes in related genes could impair platelet aggregation in patients with sticky platelet syndrome (SPS). Patients with SPS who experienced fetal loss were shown to harbor a risk haplotype at GP6 locus. The aim of the study was to examine the genetic linkage of this selected risk haplotype with single nucleotide variations (SNVs) in the coding sequence of the GP6 gene in order to identify possible functional SNVs in association with SPS and fetal loss. A total of 37 patients with SPS manifested fetal loss, and 42 healthy controls were enrolled in the study. The SPS was diagnosed with platelet aggregometry. The SNVs were determined by dideoxy sequencing and high-resolution melting analysis. The missense variations were detected in patients with risk haplotype only. The association analysis showed association of the minor alleles with the SPS manifested by fetal loss as follows-rs1671152 (odds ratio [OR]: 4.667, 95% confidence interval [CI]: 1.462-14.89, P = .006), rs2304167 (OR: 5.085, 95% CI: 1.605-16.10, P = .003), and rs1654416 (OR: 5.085, 95% CI: 1.605-16.10, P = .003). Using the Expectation-Maximization (EM) algorithm, the estimated minor haplotype with predicted protein residue PEAN was significantly associated with the given phenotype (OR: 4.746, 95% CI: 1.486-15.15, P = .005). We have shown that haplotype PEAN associated with SPS and manifested by fetal loss and suggest that the mechanism involved in the action of GPVI has significant effect on GPVI-mediated signal transduction through Syk-phosphorylation.

Introduction: Thrombophilia increases the risk of venous thrombosis during pregnancy and may predispose to gestational vascular complications., Objective: The aim of this study is to evaluate the variability of GP6 regulatory regions in a group of patients with platelet hyperaggregability manifested as miscarriage compared with control subjects., Methods: We examined 27 female patients with platelet hyperaggregability and history of spontaneous abortion and 42 healthy women. Platelet hyperaggregability was established by light transmission aggregometry. We also assessed eight SNPs within the GP6 gene., Results: We found a higher occurrence of three SNPs in patients with platelet hyperaggregability and history of miscarriage (rs1671152, rs1654433, rs1671215). The haplotype analysis showed a significant higher occurrence of two haplotypes (ACGG, CCGT)., Conclusions: Our results support the idea that genetic variability of GP6 regulatory regions can be associated with platelet hyperaggregability - a possible cause of miscarriage.

Introduction: The aim of this study was to evaluate the genetic variability of selected single nucleotide polymorphisms (SNPs) within GAS6 and PEAR1 genes and explore the association between selected SNPs and risk for fetal loss in women with sticky platelet syndrome (SPS)., Materials and Methods: We examined 23 female patients with SPS and history of spontaneous abortion, and 42 healthy women who served as controls. The diagnosis of SPS was established by light transmission aggregometry according to methods and criteria developed by Mammen et al. We also assessed four SNPs within the GAS6 gene (rs7400002, rs1803628, rs8191974, rs9550270) and two SNPs within PEAR1 gene (rs12041331, rs12566888)., Results: We identified two SNPs within PEAR1 gene (rs12041331, rs12566888) and one SNP within GAS6 gene (rs9550270) that have higher occurrence in SPS patients with history of abortion. An increased risk for abortion was observed in carriers of the rs7400002 within GAS6 gene. Conversely, we found that the T allele of PEAR1 c. -9-4663G > T polymorphism appears to be protective for fetal loss., Conclusion: Our results support the idea that genetic variability of GAS6 and PEAR1 genes may be associated with platelet hyperaggregability. The study also suggests a possible polygenic type of SPS heredity., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Objective: To evaluate the GP6 gene polymorphism in patients with sticky platelet syndrome (SPS) and fetal loss., Design: Genetic association study., Setting: Perinatal center., Patient(s): Twenty-seven patients with SPS, manifested as fetal loss, and 42 control subjects without SPS and no history of fetal loss and thrombosis., Intervention(s): SPS was diagnosed by platelet aggregometry (PACKS-4 aggregometer; Helena Laboratories). Seven single-nucleotide polymorphisms (SNPs) of the GP6 gene were evaluated., Main Outcome Measure(s): Occurrence of SNPs of the GP6 gene in SPS patients versus control subjects., Result(s): We found a higher occurrence of three SNPs of the GP6 gene in SPS patients versus control subjects (rs1671153: 0.204 vs. 0.048, odds ratio [OR] 5.116, 95% confidence interval [CI] 1.536-17.03; rs1654419: 0.204 vs. 0.071, OR 3.326, 95% CI 1.149-9.619; rs1613662: 0.204 vs. 0.071, OR 3.326, 95% CI 1.149-9.619). The haplotype analysis showed a significantly higher occurrence of two haplotypes (CTGAG in haplotype 5: 0.185 vs. 0.059, OR 3.568, 95% CI 1.142-11.14; and CGATAG in haplotype 6: 0.204 vs. 0.048, OR 4.961, 95% CI 1.488-16.53)., Conclusion(s): Our results, especially the higher occurrence of haplotypes CTGAG and CGATAG in SPS patients, support the idea that GP6 gene polymorphism may be associated with platelet hyperaggregability, a possible cause of fetal loss., (Copyright © 2012 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)