Department of Medicine, Faculté de Médecine de l'Université Laval, CHUQ Research center and Division of Rheumatology, CHUQ, Quebec City, QC, Canada.
Clin Exp Rheumatol. 2013 Sep-Oct;31(5):770-2. Epub 2013 May 28.
Beyond their role in haemostasis, platelets can actively contribute to immunity. The activation of the platelet collagen receptor glycoprotein VI (GPVI) promotes the release of small extracellular vesicles called microparticles. These microparticles are found in the joint bathing fluid of patients with rheumatoid arthritis (RA) and are thought to amplify inflammation. The gene coding for GPVI is localised on chromosome 19q13.4 and contains different single nucleotide polymorphisms (SNPs). Five non-synonymous SNPs define the major and minor haplotypes of GPVI. The minor haplotype is associated with higher risk of cardiovascular incidents. In this study, we examined whether this minor haplotype is also associated with RA.
Allelic discrimination of the SNPs reported to define these haplotypes encoding SKTQH and PEALN protein isoforms, ie rs1613662, rs1654416, rs2304167, rs1654413 and rs1671152, was performed in 399 RA patients and their two parents, all of Western European ethnicity. Statistical analysis relied on the transmission disequilibrium test by the use of the FBAT programme. Haplotypes were also estimated by the FBAT programme.
We observed no statistically significant transmission disequilibrium for the SNPs tested. The major haplotype TAAC, which encodes the SKTQH isoform, was identified in 78% of our cohort individuals, and the CGGA haplotype which encodes the PEALN isoform was identified in 8% of our individuals. We observed no association of these haplotypes of the GPVI gene with RA.
This demonstrates that the SNPs tested within the GPVI gene are not associated with RA susceptibility and/or severity, suggesting that platelet GPVI may contribute to arthritis independently of its gene polymorphism.
血小板除了在止血中发挥作用外，还能积极参与免疫。血小板胶原受体糖蛋白 VI（GPVI）的激活促进了小细胞外囊泡（称为微泡）的释放。这些微泡存在于类风湿关节炎（RA）患者的关节液中，被认为会放大炎症。编码 GPVI 的基因位于 19q13.4 染色体上，包含不同的单核苷酸多态性（SNP）。五个非同义 SNP 定义了 GPVI 的主要和次要单倍型。次要单倍型与心血管事件的风险增加相关。在这项研究中，我们研究了这种次要单倍型是否也与 RA 相关。
对报道的定义这些编码 SKTQH 和 PEALN 蛋白异构体的单倍型的 SNP（rs1613662、rs1654416、rs2304167、rs1654413 和 rs1671152）进行了等位基因鉴别，在 399 名 RA 患者及其双亲中进行了检测，他们均具有西欧血统。统计分析依赖于 FBAT 程序的传递不平衡检验。FBAT 程序还用于估计单倍型。
我们没有观察到测试 SNP 的统计学显著传递不平衡。我们队列中 78%的个体携带编码 SKTQH 异构体的主要单倍型 TAAC，而编码 PEALN 异构体的 CGGA 单倍型在 8%的个体中被识别。我们没有观察到这些 GPVI 基因单倍型与 RA 之间存在关联。
这表明，在 GPVI 基因中测试的 SNP 与 RA 的易感性和/或严重程度无关，这表明血小板 GPVI 可能独立于其基因多态性而导致关节炎。
