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  • Title: [Association of ICOS and CD28 single nucleotide polymorphisms with pulmonary tuberculosis susceptibility].
    Author: Zhang X, Ji JM, Li Q, Hua TQ, Yao P, Jiang JY, Li SS, Wang FM.
    Journal: Zhonghua Yi Xue Za Zhi; 2019 Nov 26; 99(44):3466-3470. PubMed ID: 31826563.
    Abstract:
    Objective: To investigate the association of inducible co-stimulator (ICOS) and CD28 gene polymorphisms with pulmonary tuberculosis susceptibility. Methods: In this case-control study, from Mar 2015 to Sep 2016, peripheral venous blood of 100 pulmonary tuberculosis patients (pulmonary tuberculosis group) in the Jintan People's Hospital of Changzhou and 100 community physical examination volunteers (health control group) were collected. A total of 56 single nucleotide polymorphisms (SNP) in ICOS and CD28 sequences were selected and SNP genotype and allele frequency were analyzed using the next-generation sequencing technology. Association of these SNP with pulmonary tuberculosis susceptibility was investigated using linkage disequilibrium (LD) analysis and genetic models. Results: Among these 56 SNP, 23 SNP with Hardy-Weinberg equilibrium P (HWE-P) value<0.001 or minimum allele frequency<0.05 were kicked out. The frequencies of T allele and TT genotype of ICOS gene SNP locus (rs55663036), and GG genotype of CD28 gene locus (rs45620941) in tuberculosis group were significantly higher than those in healthy control group (all P<0.05). There was a strong linkage imbalance between rs45620941 at CD28 locus and rs56262258 (r(2)=0.757). Conclusion: The polymorphisms of rs55663036 of ICOS gene and rs45620941 of CD28 gene are significantly associated with the risk of pulmonary tuberculosis. 目的： 探讨可诱导共刺激分子（ICOS）和CD28基因多态性与肺结核易感性的相关性。 方法： 采用病例-对照研究方法，采集2015年3月至2016年9月江苏省常州市金坛区人民医院就诊的100例肺结核患者（肺结核组）和100名社区健康体检者（健康对照组）的外周静脉血。采用高通量测序方法，对56个ICOS和CD28基因的单核苷酸多态性（SNP）位点进行基因分型以及连锁不平衡分析和遗传模块分析，探讨两组SNP基因型和等位基因频率的差异。 结果： 共23个SNP被剔除[哈温平衡卡方检验P值（HWE-P）<0.001或者最小等位基因频率<0.05]。肺结核组ICOS基因SNP位点（rs55663036）的T等位基因频率、TT基因型和CD28基因位点（rs45620941）的GG基因型的频率显著高于健康对照组（均P<0.05）。CD28基因rs45620941与rs56262258位点具有较强的连锁不平衡关系（r(2)=0.757）。 结论： ICOS基因rs55663036位点和CD28基因rs45620941位点的多态性与肺结核发病风险显著关联。.
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