Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, No. 37, Guo Xue Alley, Chengdu, 610041, Sichuan Province, People's Republic of China.
BMC Infect Dis. 2018 Nov 13;18(1):561. doi: 10.1186/s12879-018-3485-y.
Toll-like receptor (TLR) single nucleotide polymorphisms (SNPs) have been associated with regulation of TLR expression and development of active tuberculosis (TB). The objectives of this study were to determine whether TLR8 and TLR9 SNPs were associated with the development of latent TB infection (LTBI) and the subsequent pulmonary TB (PTB) in a Chinese Han population.
Two independent samples were enrolled. The first sample contained 584 TB cases and 608 controls; the second sample included 204 healthy controls, 201 LTBI subjects and 209 bacteria-confirmed active PTB patients. Three SNPs (rs3764880, rs187084 and rs5743836) were genotyped. The associations between the SNPs and risk of LTBI or PTB were investigated using unconditional logistic regression analysis.
The A-allele of TLR8 rs3764880 SNP was protective against the development of TB in males (A vs G, OR = 0.58, 95%CI = 0.37-0.91). The AA genotype of rs3764880 SNP was found to increase the risk of PTB among females with an OR of 4.81 (1.11-20.85). The G allele of TLR9 SNP rs187084 was found to increase the risk of PTB (G vs A, P = 0.01, OR = 1.48, 95% CI = 1.10-2.00), the significance was also observed under dominant genetic models. The GA-genotype of TLR9 rs187084 SNP was found to increase the risk of PTB with an OR of 1.68 (1.07-2.65), but was found to decrease the risk of MTB infection with an OR = 0.64 (0.41-0.98). TLR9_rs5743836 SNP was excluded from the data analyses, because the minimum allele frequency was< 1%.
Our findings in two independent samples indicated that SNPs in TLR8 and TLR9 were associated with the development of TB, and highlight that SNPs may have different effects on disease pathogenesis and progression.
Toll 样受体（TLR）单核苷酸多态性（SNP）与 TLR 表达的调节和活动性肺结核（TB）的发展有关。本研究的目的是确定 TLR8 和 TLR9 SNP 是否与中国汉族人群中潜伏性 TB 感染（LTBI）的发展以及随后的肺结核（PTB）有关。
纳入了两个独立的样本。第一个样本包含 584 例 TB 病例和 608 例对照；第二个样本包括 204 例健康对照、201 例 LTBI 受试者和 209 例经细菌证实的活动性 PTB 患者。对三个 SNP（rs3764880、rs187084 和 rs5743836）进行了基因分型。采用非条件 logistic 回归分析探讨 SNP 与 LTBI 或 PTB 风险之间的关系。
TLR8 rs3764880 SNP 的 A 等位基因对男性 TB 的发病具有保护作用（A 对 G，OR=0.58，95%CI=0.37-0.91）。rs3764880 SNP 的 AA 基因型被发现会增加女性患 PTB 的风险，比值比为 4.81（1.11-20.85）。TLR9 SNP rs187084 的 G 等位基因增加了患 PTB 的风险（G 对 A，P=0.01，OR=1.48，95%CI=1.10-2.00），在显性遗传模型下也观察到了这种显著性。TLR9 rs187084 SNP 的 GA 基因型增加了患 PTB 的风险，比值比为 1.68（1.07-2.65），但降低了 MTB 感染的风险，比值比为 0.64（0.41-0.98）。TLR9_rs5743836 SNP 被排除在数据分析之外，因为最小等位基因频率<1%。
我们在两个独立样本中的发现表明，TLR8 和 TLR9 中的 SNP 与 TB 的发生有关，并强调 SNP 可能对疾病的发病机制和进展有不同的影响。
