Xu Yanmei, Li Jing, Yang Wentao, Tang Xiaoli, Huang Bo, Liu Jing, Lin Jin, Zhang Jing, Yang Weiming, Li Shuqi, Sun Fan, Deng Libin, Wang Xiaozhong
Department of Clinical Laboratory, Jiangxi Province Key Laboratory of Laboratory Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang 330006, China.
Department of Clinical Laboratory, The First Affiliated Hospital of Nanchang University, Nanchang 330006, China.
Int J Genomics. 2020 Mar 11;2020:7531876. doi: 10.1155/2020/7531876. eCollection 2020.
Immune thrombocytopenia (ITP) is an acquired bleeding disease due to immune-mediated destruction of antilogous platelets and ineffective thrombopoiesis. Although the etiology of ITP remains unknown, genetic variants are thought to predispose individuals to the disease. Several candidate gene analyses have identified several loci that increased ITP susceptibility, but no systematic genetic analysis on a genome-wide scope. To extend the genetic evidence and to identify novel candidates of ITP, we performed a pooling genome-wide association study (GWAS) by IlluminaHumanOmniZhongHua-8 combining pathway analysis in 200 ITP cases and 200 controls from Chinese Han population (CHP). The results revealed that 4 novel loci (rs117503120, rs5998634, rs4483616, and rs16866133) were strongly associated with ITP ( < 1.0 × 10). Expect for rs4483616, other three loci were validated by the TaqMan probe genotyping assay ( < 0.05) in another cohort including 250 ITP cases and 250 controls. And rs5998634 T allele was more sensitive to glucocorticoids for ITP patients ( = 7.30, < 0.05). Moreover, we identified three overrepresented signaling pathways including the neuroactive ligand-receptor interaction, pathways in cancer, and the JAK-STAT pathway, which involved in the etiology of ITP. In conclusion, our results revealed four novel loci and three pathways related to ITP and provided new clues to explore the pathogenesis of ITP.
免疫性血小板减少症（ITP）是一种获得性出血性疾病，由于免疫介导的自身血小板破坏和血小板生成无效所致。尽管ITP的病因尚不清楚，但遗传变异被认为使个体易患该病。几项候选基因分析已经确定了几个增加ITP易感性的基因座，但尚未进行全基因组范围的系统遗传分析。为了扩展遗传证据并识别ITP的新候选基因，我们通过IlluminaHumanOmniZhongHua-8对来自中国汉族人群（CHP）的200例ITP病例和200例对照进行了混合全基因组关联研究（GWAS）并结合通路分析。结果显示，4个新的基因座（rs117503120、rs5998634、rs4483616和rs16866133）与ITP密切相关（<1.0×10）。除rs4483616外，其他三个基因座在另一个包含250例ITP病例和250例对照的队列中通过TaqMan探针基因分型检测得到验证（<0.05）。并且rs5998634的T等位基因对ITP患者的糖皮质激素更敏感（=7.30，<0.05）。此外，我们确定了三个过度表达的信号通路，包括神经活性配体-受体相互作用、癌症通路和JAK-STAT通路，它们参与了ITP的病因。总之，我们的结果揭示了与ITP相关的四个新基因座和三个通路，并为探索ITP的发病机制提供了新线索。
