Harishankar Murugesan, Selvaraj Paramasivam, Bethunaickan Ramalingam
Department of Immunology, National Institute of Research in Tuberculosis, Chennai, India.
Front Med (Lausanne). 2018 Aug 16;5:213. doi: 10.3389/fmed.2018.00213. eCollection 2018.
Tuberculosis (TB) is still remains the major threat for human health worldwide. Several case-control, candidate-gene, family studies and genome-wide association studies (GWAS) suggested the association of host genetic factors to TB susceptibility or resistance in various ethnic populations. Moreover, these factors modulate the host immune responses to tuberculosis. Studies have reported genetic markers to predict TB development in human leukocyte antigen (HLA) and non-HLA genes like killer immunoglobulin-like receptor (KIR), toll-like receptors (TLRs), cytokine/chemokines and their receptors, vitamin D receptor (VDR) and SLC11A1 etc. Highly polymorphic HLA loci may influence antigen presentation specificities by modifying peptide binding motifs. The recent meta-analysis studies revealed the association of several HLA alleles in particular class II HLA-DRB1 with TB susceptibility and valuable marker for disease development especially in Asian populations. Case-control studies have found the association of HLA-DR2 in some populations, but not in other populations, this could be due to an ethnic specific association of gene variants. Recently, GWAS conducted in case-control and family based studies in Russia, Chinese Han, Morocco, Uganda and Tanzania revealed the association of genes such as () and intergenic SNP rs932347C/T with TB. Whereas, SNP rs10956514A/G were not associated with TB in western Chinese Han and Tibetan population. In this review, we summarize the recent findings of genetic variants with susceptibility/resistance to TB.
结核病（TB）仍然是全球人类健康的主要威胁。多项病例对照研究、候选基因研究、家族研究以及全基因组关联研究（GWAS）表明，宿主遗传因素与不同种族人群对结核病的易感性或抵抗力有关。此外，这些因素调节宿主对结核病的免疫反应。研究报告了一些遗传标记，可用于预测人类白细胞抗原（HLA）和非HLA基因（如杀伤细胞免疫球蛋白样受体（KIR）、Toll样受体（TLR）、细胞因子/趋化因子及其受体、维生素D受体（VDR）和SLC11A1等）中结核病的发展情况。高度多态的HLA基因座可能通过修饰肽结合基序来影响抗原呈递特异性。最近的荟萃分析研究揭示了几个HLA等位基因，特别是II类HLA - DRB1与结核病易感性的关联，以及对疾病发展有价值的标记，尤其是在亚洲人群中。病例对照研究在一些人群中发现了HLA - DR2的关联，但在其他人群中未发现，这可能是由于基因变异的种族特异性关联。最近，在俄罗斯、中国汉族、摩洛哥、乌干达和坦桑尼亚进行的病例对照研究和基于家族的GWAS揭示了诸如（）和基因间SNP rs932347C/T与结核病的关联。然而，SNP rs10956514A/G在中国西部汉族和藏族人群中与结核病无关。在本综述中，我们总结了近期关于结核病易感性/抗性遗传变异的研究结果。
