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Toll样受体1基因743A>G、1805T>G及Toll样受体6基因745C>T多态性与结核病:印度阿格拉北部印度人群的病例对照研究

Toll-like Receptor 1 743 A>G, 1805 T>G & Toll-like Receptor 6 745 C>T gene polymorphism and tuberculosis: a case control study of north Indian population from Agra (India).

作者信息

Sinha Ekata, Biswas Sanjay K, Mittal Mayank, Bajaj Bharat, Singh Vandana, Arela Nidhi, Katoch Vishwa M, Mohanty Keshar Kunja

机构信息

Immunology Division, National JALMA Institute for Leprosy and Other Mycobacterial Diseases, Agra, India.

State Tuberculosis Demonstration Centre (STDC), Agra, India.

出版信息

Hum Immunol. 2014 Aug;75(8):880-6. doi: 10.1016/j.humimm.2014.06.014. Epub 2014 Jun 28.

Abstract

Infection with Mycobacteriumtuberculosis possibly depends on host genetic factors and is thought to be the major cause of differential susceptibility to the disease. In the present study, 205 pulmonary tuberculosis cases and 127 healthy controls were studied for the association of Toll-like Receptor (TLR) variants (TLR1 variants 743A>G and 1805T>G, and TLR6 variant 745 C>T) in north Indian population. The frequency of heterozygous genotypes (AG) in TB cases (0.47) and HCs (0.61), differed significantly (p value = 0.02). The association of AG genotypes in HCs was adjusted for gender as gender was observed to be a confounder and M-H OR was found to be 0.62 (p = 0.044). On categorizing the cases basing on AFB smear positivity, the heterozygous genotypes (AG) was found to be associated with low bacillary load (scanty and 1+) (P = 0.002). No association was observed for either TLR1 1805 T>G or TLR6 745 C>T polymorphism. Level of serum IL6 was found to be significantly higher among healthy controls with TLR1 GG genotype compared to healthy controls with AA (p = 0.035) and AG (p = 0.005) genotypes. Thus, it may be suggested that the heterozygous condition for TLR1 743 A>G provide resistance from the disease. However, in depth study is required to understand the mechanism for possible protective responses.

摘要

结核分枝杆菌感染可能取决于宿主遗传因素,被认为是疾病易感性差异的主要原因。在本研究中,对205例肺结核病例和127名健康对照者进行了研究,以探讨北印度人群中Toll样受体(TLR)变体(TLR1变体743A>G和1805T>G,以及TLR6变体745 C>T)的关联性。肺结核病例(0.47)和健康对照者(0.61)中杂合基因型(AG)的频率差异显著(p值=0.02)。由于观察到性别是一个混杂因素,因此对健康对照者中AG基因型的关联性进行了性别调整,发现M-H比值比为0.62(p=0.044)。根据抗酸杆菌涂片阳性情况对病例进行分类时,发现杂合基因型(AG)与低细菌载量(少量和1+)相关(P=0.002)。未观察到TLR1 1805 T>G或TLR6 745 C>T多态性的关联性。与TLR1 AA基因型(p=0.035)和AG基因型(p=0.005)的健康对照者相比,TLR1 GG基因型的健康对照者血清IL6水平显著更高。因此,可能提示TLR1 743 A>G的杂合状态可提供对该疾病的抵抗力。然而,需要深入研究以了解可能的保护反应机制。

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