A CARD9 single-nucleotide polymorphism rs4077515 is associated with reduced susceptibility to and severity of primary immune thrombocytopenia
A CARD9 single-nucleotide polymorphism rs4077515 is associated with reduced susceptibility to and severity of primary immune thrombocytopenia
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CARD9 单核苷酸多态性 rs4077515 与原发性免疫性血小板减少症的易感性降低和严重程度降低相关
DOI：
10.1007/s00277-019-03796-7
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发表时间：
2019
影响因子：
3.5
通讯作者：
Feng Qi
中科院分区：
文献类型：
--
作者：
Sheng Zi;Li Ju;Wang Yuanjian;Li Song;Hou Ming;Peng Jun;Feng Qi
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，其特征是血小板计数低和随之而来的出血风险增加。这种情况的病因学仍然知之甚少。本研究的目的是评估含半胱天冬酶募集结构域的蛋白 9 (CARD9) 基因中的单核苷酸多态性 (SNP) rs4077515 与 ITP 发病机制和治疗的关联。这项病例对照研究招募了 294 名 ITP 患者和 324 名年龄匹配的健康参与者。通过Sanger测序对CARD9 rs4077515多态性进行基因分型。我们的结果显示，CARD9 基因中的 rs4077515 多态性与 ITP 易感性和严重程度降低的风险相关（易感性：共显性，AA 与 GG，OR = 0.175，95% CI = 0.054-0.776，p= 0.001；隐性，GG + AG 与 AA，OR = 6.183， 95% CI = 2.287–16.715，p< 0.001；严重性：等位基因，A 与 G，OR = 0.685，95% CI = 0.476–0.985，p= 0.041；共显性，AG 与 GG，OR = 0.571，95% CI = 0.350–0.931，p= 0.025；占主导地位，AA + AG 与 GG，OR = 0.558，95% CI = 0.343–0.907，p= 0.019）。 CARD9 rs4077515的等位基因A、突变AA基因型和杂合AG基因型的存在，在ITP中发挥保护作用。然而，CARD9 rs4077515 多态性对皮质类固醇敏感性或 ITP 难治性没有影响。
Primary immune thrombocytopenia (ITP) is an acquired autoimmune disease characterized by a low platelet count and consequent increased risk of bleeding. The etiology underlying this condition remains poorly understood. The aim of this study is to evaluate the association of a single nucleotide polymorphism (SNP) rs4077515 in the caspase recruitment domain-containing protein 9 (CARD9) gene with the pathogenesis and therapy of ITP. Two hundred ninety-four patients with ITP and 324 age-matched healthy participants were recruited in this case-control study. Genotyping of CARD9 rs4077515 polymorphism was performed by Sanger sequencing. Our results revealed that a polymorphism rs4077515 in CARD9 gene is associated with decreased risk of susceptibility to and severity of ITP (susceptibility: codominant, AA vs. GG, OR = 0.175, 95% CI = 0.054-0.776,p= 0.001; recessive, GG + AG vs. AA, OR = 6.183, 95% CI = 2.287–16.715,p< 0.001; severity: allele, A vs. G, OR = 0.685, 95% CI = 0.476–0.985,p= 0.041; codominant, AG vs. GG, OR = 0.571, 95% CI = 0.350–0.931,p= 0.025; dominant, AA + AG vs. GG, OR = 0.558, 95% CI = 0.343–0.907,p= 0.019). The existence of the allele A, the mutant AA genotype and the heterozygous AG genotype of CARD9 rs4077515, plays a protective role in ITP. However, CARD9 rs4077515 polymorphism had no effect on corticosteroid sensitivity or refractoriness of ITP.