变体rs5743557与结核病易感性的关联。
Association of the variant rs5743557 with susceptibility to tuberculosis.
作者信息
Zhang Miaomiao, Wang Jing, Wang Yu, Wu Shouquan, Sandford Andrew J, Luo Jun, He Jian-Qing
机构信息
Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu 610041, China.
Division of Infectious Diseases, People's Hospital of Aba Tibetan Autonomous Prefecture, Aba Autonomous 624000, China.
出版信息
J Thorac Dis. 2019 Feb;11(2):583-594. doi: 10.21037/jtd.2019.01.74.
BACKGROUND
Toll-like receptor 1 (TLR1) and TLR6 play important roles in the innate immune response against (M.TB) via interactions with TIR domain-containing adaptor protein (TIRAP) and myeloid differentiation primary response 88 (MYD88). The aim of this study was to investigate the relationship of and polymorphisms with susceptibility to latent tuberculosis infection (LTBI) and tuberculosis (TB).
METHODS
In total, 204 uninfected healthy controls (HC), 201 individuals with LTBI and 209 TB patients were enrolled. Two interferon-γ release assays were used to differentiate individuals with LTBI from uninfected controls. TagSNPs of the four genes were genotyped by the SNPscan Kit. The Haploview 4.2 and SHEsis software packages were combined to perform linkage disequilibrium (LD) and haplotype analyses. Multifactor dimensionality reduction (MDR) software was used to investigate gene-gene interaction. The Stata 12.0 software was used to perform meta-analysis of the relationship between rs5743557 and TB susceptibility.
RESULTS
The AA genotype of rs5743557 was associated with reduced TB risk (P=0.006) and the AA/GA genotypes of rs5743604 were associated with increased TB risk (P=0.017) when the LTBI group was compared with the TB group. The frequency of haplotype rs4833095-rs5743604 CG was significantly higher in the LTBI group than in the TB group (P=0.019877). However, only the relationship between rs5743557 and TB susceptibility remained significant after 1000-fold permutation testing (P=0.023). The meta-analysis suggested that rs5743557_A was associated with decreased TB risk in the Chinese adult population (P<0.001, OR 0.80, 95% CI: 0.72-0.88). No significant gene-gene interactions were found.
CONCLUSIONS
The results of our study suggest that the tagSNP rs5743557 of is associated with the risk of TB.
背景
Toll样受体1（TLR1）和TLR6通过与含TIR结构域的接头蛋白（TIRAP）和髓样分化初级反应蛋白88（MYD88）相互作用，在针对结核分枝杆菌（M.TB）的固有免疫反应中发挥重要作用。本研究旨在探讨TLR1和TLR6基因多态性与潜伏性结核感染（LTBI）及结核病（TB）易感性之间的关系。
方法
共纳入204名未感染的健康对照（HC）、201名LTBI患者和209名TB患者。采用两种干扰素-γ释放试验区分LTBI患者和未感染对照。通过SNPscan试剂盒对四个基因的标签单核苷酸多态性（TagSNP）进行基因分型。结合Haploview 4.2和SHEsis软件包进行连锁不平衡（LD）和单倍型分析。使用多因素降维（MDR）软件研究基因-基因相互作用。运用Stata 12.0软件对rs5743557与TB易感性之间的关系进行荟萃分析。
结果
与TB组相比，在LTBI组中，rs5743557的AA基因型与TB风险降低相关（P = 0.006），rs5743604的AA/GA基因型与TB风险增加相关（P = 0.017）。LTBI组中rs4833095 - rs5743604单倍型CG的频率显著高于TB组（P = 0.019877）。然而，经过1000次置换检验后，只有rs5743557与TB易感性之间的关系仍然显著（P = 0.023）。荟萃分析表明，在中国成年人群中，rsA5743557与TB风险降低相关（P < 0.001，比值比0.80，95%可信区间：0.72 - 0.88）。未发现显著的基因-基因相互作用。
结论
我们的研究结果表明，TLR1基因的标签单核苷酸多态性rs5743557与TB风险相关。
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