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白细胞介素17A和白细胞介素6中的单核苷酸多态性与巴西南部人群患肺结核风险降低相关。

Single Nucleotide Polymorphisms in IL17A and IL6 Are Associated with Decreased Risk for Pulmonary Tuberculosis in Southern Brazilian Population.

作者信息

Milano Mariana, Moraes Milton Ozório, Rodenbusch Rodrigo, Carvalho Caroline Xavier, Delcroix Melaine, Mousquer Gabriel, Laux da Costa Lucas, Unis Gisela, Dalla Costa Elis Regina, Rossetti Maria Lucia Rosa

机构信息

Programa de Pós-Graduação em Biologia Celular e Molecular, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.

Centro de Desenvolvimento Científico e Tecnológico, Fundação Estadual de Produção e Pesquisa em Saúde, Porto Alegre, Rio Grande do Sul, Brazil.

出版信息

PLoS One. 2016 Feb 3;11(2):e0147814. doi: 10.1371/journal.pone.0147814. eCollection 2016.

Abstract

In Mycobacterium tuberculosis (MTB) infection, the complex interaction of host immune system and the mycobacteria is associated with levels of cytokines production that play a major role in determining the outcome of the disease. Several single-nucleotide polymorphisms (SNPs) in cytokine genes have been associated with tuberculosis (TB) outcome. The aim of this study was to evaluate the association between previously reported SNPs IL2-330 T>G (rs2069762); IL4-590 C>T (rs2243250); IL6-174 G>C (rs1800795); IL10-592 A>C (rs1800872); IL10-1082 G>A (rs1800896); IL17A -692 C>T (rs8193036); IL17A -197 G>A (rs2275913); TNF -238 G>A (rs361525); TNF -308 G>A (rs1800629) and IFNG +874 T>A (rs2430561) and pulmonary TB (PTB) susceptibility. We conducted a case-control study in individuals from Southern Brazil who were recruited between February 2012 and October 2013 in a high incidence TB city. We performed a multiplex genotyping assay in 191 patients with PTB and 175 healthy subjects. Our results suggest a decreased risk for PTB development associated with the IL17A -197A allele (OR = 0.29; p = 0.04), AA genotype (OR = 0.12; p = 0.04) and A carrier (AG/AA) (OR = 0.29; p = 0.004) and IL6 -174C carrier (CC/CG) (OR = 0.46; p = 0.04). We could not properly analyze IL17A -692 C>T (rs8193036) and IFNG +874T>A due to genotypic inconsistencies and found no evidence of association for the IL2, IL4, IL10 and TNF polymorphisms and PTB. In conclusion, our results show a protective effect of IL17 and IL6 polymorphisms on PTB outcome in Southern Brazilian population.

摘要

在结核分枝杆菌(MTB)感染中,宿主免疫系统与分枝杆菌之间复杂的相互作用与细胞因子的产生水平相关,而细胞因子在决定疾病的转归中起主要作用。细胞因子基因中的几个单核苷酸多态性(SNP)与结核病(TB)的转归有关。本研究的目的是评估先前报道的单核苷酸多态性IL2 - 330 T>G(rs2069762);IL4 - 590 C>T(rs2243250);IL6 - 174 G>C(rs1800795);IL10 - 592 A>C(rs1800872);IL10 - 1082 G>A(rs1800896);IL17A - 692 C>T(rs8193036);IL17A - 197 G>A(rs2275913);TNF - 238 G>A(rs361525);TNF - 308 G>A(rs1800629)和IFNG + 874 T>A(rs2430561)与肺结核(PTB)易感性之间的关联。我们对2012年2月至2013年10月在一个结核病高发城市招募的巴西南部个体进行了一项病例对照研究。我们对191例PTB患者和175名健康受试者进行了多重基因分型检测。我们的结果表明,IL17A - 197A等位基因(OR = 0.29;p = 0.04)、AA基因型(OR = 0.12;p = 0.04)以及A携带者(AG/AA)(OR = 0.29;p = 0.004)和IL6 - 174C携带者(CC/CG)(OR = 0.46;p = 0.04)与PTB发病风险降低相关。由于基因分型不一致,我们无法对IL17A - 692 C>T(rs8193036)和IFNG + 874T>A进行恰当分析,并且未发现IL2、IL4、IL10和TNF多态性与PTB相关的证据。总之,我们的结果显示IL17和IL6多态性对巴西南部人群的PTB转归具有保护作用。

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