Genetic contribution of CISH promoter polymorphisms to susceptibility to tuberculosis in Chinese children.
Genetic contribution of CISH promoter polymorphisms to susceptibility to tuberculosis in Chinese children.
复制标题
CISH启动子多态性对中国儿童结核病易感性的遗传贡献
DOI：
10.1371/journal.pone.0092020
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Shen AD
中科院分区：
文献类型：
--
作者：
Sun L;Jin YQ;Shen C;Qi H;Chu P;Yin QQ;Li JQ;Tian JL;Jiao WW;Xiao J;Shen AD
结核病 (TB) 是世界范围内传染病导致死亡的主要原因，特别是在发展中国家。一系列候选基因被认为与结核病的发生有关。其中，人类细胞因子诱导的Src同源2（SH2）结构域蛋白（CISH）基因最近被报道参与响应结核分枝杆菌感染的T细胞活化和分化。在这里，我们研究了 CISH 启动子多态性与儿童结核病之间的关联。一项病例对照研究纳入了 352 名结核病患者和 527 名健康对照，他们都是汉族，年龄从 0.2 岁到 18 岁。对所有受试者进行CISH基因启动子SNP rs414171、rs622502和rs809451的基因分型，并进一步检测不同基因型受试者的转录活性、mRNA水平和血浆细胞因子水平。与野生型基因型携带者相比，rs414171TT 纯合子和 rs809451GC 杂合子携带者患结核病的风险分别高出 1.78 倍（95% CI，1.16–2.74）和 1.86 倍（95% CI，1.26–2.74）。在携带 C−809451-T−414171-C−622502 单倍型的人群中观察到患结核病的风险较高（OR 3.66，95% CI：2.12–6.32）。与 Hela 细胞系中含有 C−809451-T−414171-C−622502 的对应启动子相比，含有 G−809451-A−414171-C−622502 的 CISH 启动子驱动的报告基因表达增加了 5.43 倍（P = 0.0009）。与携带野生型基因型的细胞相比，携带 rs414171TT 纯合子和 rs809451GC 杂合子的 PBMC 显示出 CISH mRNA 水平降低。具有 rs414171TT 基因型的个体 IL-12p40 和 IL-10 的产生显着增加。总之，CISH启动子rs414171和rs809451多态性可能在介导个体对结核病的易感性中发挥重要作用。
Tuberculosis (TB) is the leading cause of death due to an infectious disease worldwide, particularly in developing countries. A series of candidate genes have been suggested to be associated with development of TB disease. Among them, the human Cytokine-inducible Src homology 2(SH2) domain protein (CISH) gene has been very recently reported to be involved in T cell activation and differentiation in response to Mycobacterium tuberculosis infection. Here, we studied the association between CISH promoter polymorphisms and pediatric TB. A case-control study enrolled 352 TB patients and 527 healthy controls, who were of Han Chinese ethnicity and aged from 0.2 to 18 years. CISH gene promoter SNPs rs414171, rs622502 and rs809451 were genotyped in all subjects and transcriptional activity, mRNA level, and plasma cytokine level of subjects with different genotypes were further examined. Carriers with rs414171TT homozygotes and rs809451GC heterozygotes had a 1.78-fold (95% CI,1.16–2.74) and 1.86-fold (95% CI, 1.26–2.74) excess risk of developing TB compared to those with wild-type genotypes. A greater risk of TB disease was observed in population carrying C−809451-T−414171-C−622502 haplotype (OR 3.66, 95% CI:2.12–6.32). The G−809451-A−414171-C−622502-containing CISH promoter drove a 5.43-fold increased reporter expression compared to the C−809451-T−414171-C−622502-containing counterpart in Hela cell lines (P = 0.0009). PBMCs carrying rs414171TT homozygotes and rs809451GC heterozygotes showed a reduced CISH mRNA level compared to cells carrying wild type genotypes. Individuals with the rs414171TT genotype had significantly increased IL-12p40 and IL-10 production. In conclusion, CISH promoter rs414171 and rs809451 polymorphisms may play a vital role in mediating individual susceptibility to tuberculosis.
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影响因子：
0.4
作者：
Bahari, G.;Hashemi, M.;Eskandari-Nasab, E.
通讯作者：
Eskandari-Nasab, E.
影响因子：
4.4
作者：
Russell, TD;Yan, QY;Walter, MJ
通讯作者：
Walter, MJ
影响因子：
3.7
作者：
Nolan A;Fajardo E;Huie ML;Condos R;Pooran A;Dawson R;Dheda K;Bateman E;Rom WN;Weiden MD
通讯作者：
Weiden MD
DOI：
10.4149/bll_2012_148
发表时间：
2012-01-01
影响因子：
1.5
作者：
Hanta, I;Tastemir-Korkmaz, D.;Seydaoglu, G.
通讯作者：
Seydaoglu, G.
DOI：
10.1056/nejmoa0905606
发表时间：
2010-06-03
期刊：
The New England journal of medicine
影响因子：
--
作者：
Khor CC;Vannberg FO;Chapman SJ;Guo H;Wong SH;Walley AJ;Vukcevic D;Rautanen A;Mills TC;Chang KC;Kam KM;Crampin AC;Ngwira B;Leung CC;Tam CM;Chan CY;Sung JJ;Yew WW;Toh KY;Tay SK;Kwiatkowski D;Lienhardt C;Hien TT;Day NP;Peshu N;Marsh K;Maitland K;Scott JA;Williams TN;Berkley JA;Floyd S;Tang NL;Fine PE;Goh DL;Hill AV
通讯作者：
Hill AV