Inflammation-Related Gene Polymorphisms Associated With Primary Immune Thrombocytopenia.
Inflammation-Related Gene Polymorphisms Associated With Primary Immune Thrombocytopenia.
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与原发性免疫性血小板减少症相关的炎症相关基因多态性
DOI：
10.3389/fimmu.2017.00744
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发表时间：
2017
影响因子：
7.3
通讯作者：
Peng J
中科院分区：
文献类型：
--
作者：
Li J;Ma S;Shao L;Ma C;Gao C;Zhang XH;Hou M;Peng J
原发性免疫性血小板减少症(ITP)是一种获得性自身免疫性疾病，以血小板数量减少和出血风险增加为特征。虽然大量的研究提高了我们对ITP的认识，但其发病机制仍不清楚。在这里，我们研究了炎症相关基因CD24、CD226、FCRL3、IL2、IRF5、ITGAM、NLRP3、CARD8、PTPN22、SH2B2、STAT4、TNFAIP3和TRAF1的25个单核苷酸多态性(SNPs)在ITP的发病和治疗反应中的作用。在这项病例对照研究中，我们招募了312名ITP住院患者和154名健康参与者。在Sequenom Massarray IPLEX平台上进行炎症相关SNP基因分型。用实时荧光定量RT-PCR方法检测TNFAIP3基因的表达。健康对照组的所有SNP均符合Hardy-Weinberg平衡。统计分析显示，TNFAIP3基因rs10499194与Bonferroni多重矫正后ITP的风险降低显著相关(共显性，CT与CC，OR = 0.431，95%CI = 0.262~0.711，p = 0.001；显性，TT/CT vs CC，OR = 0.249，95%CI = 0.141~0.440，p = 0.000)。此外，CT和混合CT/TT基因型患者的TNFAIP3表达显著高于CC基因型(p = 0.001；p = 0.001)。有趣的是，rs10499194还与激素敏感性相关(共显性，CT与CC，OR = 0.092，95%CI = 0.021-0.398，p = 0.001；显性，TT/CT与CC，OR = 0.086，95%CI = 0.020-0.369，p = 0.001；等位基因，T与C，OR = 0.088，95%CI = 0.021-0.372，p = 0001)。此外，未发现炎症相关SNPs与Bonferroni多次矫正后ITP的严重程度或难治性显著相关。我们的研究结果表明，rs10499194可能是ITP患者易感性和皮质类固醇敏感性的保护因素。
Primary immune thrombocytopenia (ITP) is an acquired autoimmune disease characterized by a reduced platelet count and an increased risk of bleeding. Although immense research has improved our understanding of ITP, the pathogenesis remains unclear. Here, we investigated the involvement of 25 single-nucleotide polymorphisms (SNPs) of the inflammation-related genes, including CD24, CD226, FCRL3, IL2, IRF5, ITGAM, NLRP3, CARD8, PTPN22, SH2B2, STAT4, TNFAIP3, and TRAF1, in the pathogenesis and treatment response of ITP. We recruited 312 ITP inpatients and 154 healthy participants in this case–control study. Inflammation-related SNP genotyping was performed on the Sequenom MassARRAY iPLEX platform. The expression of TNFAIP3 mRNA was determined by quantitative real-time RT-PCR. All SNPs in healthy controls were consistent with Hardy–Weinberg equilibrium. Statistical analysis revealed that rs10499194 in TNFAIP3 was significantly associated with a decreased risk of ITP after Bonferroni multiple correction (codominant, CT vs. CC, OR = 0.431, 95% CI = 0.262–0.711, p = 0.001; dominant, TT/CT vs. CC, OR = 0.249, 95% CI = 0.141–0.440, p = 0.000). Besides, TNFAIP3 expression was significantly higher in patients with CT and pooled CT/TT genotypes compared with CC genotype (p = 0.001; p = 0.001). Interestingly, rs10499194 was also associated with corticosteroid-sensitivity (codominant, CT vs. CC, OR = 0.092, 95% CI = 0.021–0.398, p = 0.001; dominant, TT/CT vs. CC, OR = 0.086, 95% CI = 0.020–0.369, p = 0.001; allelic, T vs. C, OR = 0.088, 95% CI = 0.021–0.372, p = 0.001). Furthermore, no significant association was found between inflammation-related SNPs and the severity or refractoriness of ITP after Bonferroni multiple correction. Our findings suggest that rs10499194 may be a protective factor for susceptibility and corticosteroid sensitivity in ITP patients.