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评估TLR2、TLR4和TOLLIP基因多态性在结核病易感性中的作用。

Evaluation of TLR2, TLR4, and TOLLIP polymorphisms for their role in tuberculosis susceptibility.

作者信息

Wu Shouquan, Huang Weiwei, Wang Dan, Wang Yu, Wang Minggui, Zhang Miaomiao, He Jian-Qing

机构信息

Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, China.

出版信息

APMIS. 2018 Jun;126(6):501-508. doi: 10.1111/apm.12855.

DOI:10.1111/apm.12855
PMID:29924447
Abstract

Previous studies indicated that single-nucleotide polymorphisms (SNPs) of genes coding for toll-like receptors (TLRs) and toll-interacting protein (TOLLIP) may be involved in the pathogenesis of pulmonary tuberculosis (PTB). This study was designed to investigate potential associations between the polymorphisms in TLR2, TLR4, and TOLLIP and susceptibility to latent tuberculosis infection (LTBI) or subsequent PTB in a Chinese Han population. A total of 209 PTB and 201 LTBI patients and 204 healthy control subjects (HCS) were enrolled in our study. We performed a logistic regression including sex and age as covariates to test the effect of genotype. Genotyping was conducted using the improved multiplex ligase detection reaction (iMLDR). Eleven markers in TLR2, TLR4, and TOLLIP were assessed. No significant association between polymorphisms of TLR2 and TLR4 with PTB or LTBI was detected. For TOLLIP, rs5743899 (p = 0.005, OR = 1.83, 95% CI: 1.20-2.80) CC genotype were risk factors for PTB progression. Moreover, rs5743867 under addictive (p = 0.005, OR = 1.54, 95% CI: 1.14-2.07) and recessive model (p = 0.004, OR = 1.86, 95% CI: 1.22-2.83) were also risk factors for PTB susceptibility. Our results indicate that polymorphisms in TOLLIP affected the risk of PTB disease.

摘要

先前的研究表明,编码Toll样受体(TLR)和Toll相互作用蛋白(TOLLIP)的基因单核苷酸多态性(SNP)可能参与了肺结核(PTB)的发病机制。本研究旨在调查TLR2、TLR4和TOLLIP基因多态性与中国汉族人群潜伏性结核感染(LTBI)易感性或随后发生PTB之间的潜在关联。我们的研究共纳入了209例PTB患者、201例LTBI患者和204例健康对照者(HCS)。我们进行了一项以性别和年龄作为协变量的逻辑回归分析,以检验基因型的影响。采用改进的多重连接酶检测反应(iMLDR)进行基因分型。评估了TLR2、TLR4和TOLLIP中的11个标记。未检测到TLR2和TLR4基因多态性与PTB或LTBI之间存在显著关联。对于TOLLIP,rs5743899(p = 0.005,OR = 1.83,95% CI:1.20 - 2.80)CC基因型是PTB进展的危险因素。此外,rs5743867在相加模型(p = 0.005,OR = 1.54,95% CI:1.14 - 2.07)和隐性模型(p = 0.004,OR = 1.86,95% CI:1.22 - 2.83)下也是PTB易感性的危险因素。我们的结果表明,TOLLIP基因多态性影响了PTB疾病的风险。

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