Soeroto Arto Yuwono, Dahlan Zulkarnain, Kartasasmita Cissy B, Parwati Ida
Department of Internal Medicine, Faculty of Medicine Universitas Padjadjaran, Bandung, Indonesia.
Acta Med Indones. 2018 Jan;50(1):53-60.
Toll-like receptor is a pattern recognition receptor (PRR) that recognize pathogen-associated molecular pattern (PAMP) in a microorganism. Macrophages recognize the presence of mycobacteria through Toll-Like Receptor 2 (TLR2) and signaling further lead to the production of cytokines, both proinflammatory TNF-α, IL-1β, IL-6, IL-12, IL-15, IL-18 and IFN-γ, as well as anti-inflammatory IL4, IL-10 and TGF-β. TLR2 gene polymorphism is strongly determined by ethnicity and geography. Therefore it is necessary to uncovered the existence and association between Arg753Gln and Arg677Trp TLR2 gene polymorphism with TB susceptibility and its underlying mechanisms in Indonesian population in Bandung West Java.
analytical observational study with cross-sectional design was conducted in Hasan Sadikin General Hospital Bandung from April 2011 to May 2012. Study population consisted of active pulmonary TB patient with positive AFB smear and Latent TB to ascertain previous MTb exposure. Polymorphism of gen Arg753Gln and Arg677Trp gene was determined with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods. Plasma levels of IFN-γ, TNF-α, IL-10 and IL-12 were also compared between active and latent TB group.
heterozygote Arg753Gln TLR2 gene polymorphism was found in 9 of 86 pulmonary TB subjects (10.5%) but none in the latent TB group. The Arg677Trp polymorphism was not found in both groups. The odds ratio for Arg753Gln existence was 28.07 (p=0.022). No differences in the levels of IFN-γ, TNF-α, IL-10 and IL-12 between active pulmonary TB and latent TB subjects with and without Arg753Gln TLR2 gene polymorphism. Conlusion: Arg753Gln polymorphism of TLR2 gene is a risk factor for active pulmonary TB while Arg677Trp polymorphism is not. The Increased risk is not mediated by the difference in IFN-γ, TNF-α, IL-10 and IL-12 serum levels.
Toll样受体是一种模式识别受体（PRR），可识别微生物中的病原体相关分子模式（PAMP）。巨噬细胞通过Toll样受体2（TLR2）识别分枝杆菌的存在，信号传导进一步导致细胞因子的产生，包括促炎细胞因子TNF-α、IL-1β、IL-6、IL-12、IL-15、IL-18和IFN-γ，以及抗炎细胞因子IL4、IL-10和TGF-β。TLR2基因多态性在很大程度上由种族和地理位置决定。因此，有必要在西爪哇万隆的印度尼西亚人群中揭示Arg753Gln和Arg677Trp TLR2基因多态性与结核病易感性之间的存在及关联及其潜在机制。
2011年4月至2012年5月在万隆哈桑·萨迪金综合医院进行了一项采用横断面设计的分析性观察研究。研究人群包括痰涂片抗酸杆菌阳性的活动性肺结核患者和潜伏性结核患者，以确定既往是否感染过结核分枝杆菌（MTb）。采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）方法测定Arg753Gln和Arg677Trp基因的多态性。还比较了活动性结核组和潜伏性结核组之间血浆IFN-γ、TNF-α、IL-10和IL-12水平。
在86例肺结核患者中有9例（10.5%）发现了杂合子Arg753Gln TLR2基因多态性，而潜伏性结核组未发现。两组均未发现Arg677Trp多态性。Arg753Gln存在的比值比为28.07（p=0.022）。有无Arg753Gln TLR2基因多态性的活动性肺结核患者和潜伏性结核患者之间，IFN-γ、TNF-α、IL-10和IL-12水平无差异。结论：TLR2基因的Arg753Gln多态性是活动性肺结核的危险因素，而Arg677Trp多态性不是。风险增加并非由IFN-γ、TNF-α、IL-10和IL-12血清水平的差异介导。
