背景:Toll样受体(TLR)单核苷酸多态性(SNP)与TLR表达的调节和活动性结核病(TB)的发展有关。这项研究的目的是确定TLR8和TLR9SNP是否与中国汉族人群中潜伏性结核病感染(LTBI)和随后的肺结核(PTB)的发展有关。
方法:纳入两个独立样本。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名LTBI受试者和209名细菌确认的活动性PTB患者。对三个SNPs(rs3764880、rs187084和rs5743836)进行基因分型。使用非条件逻辑回归分析研究SNP与LTBI或PTB风险之间的关联。
结果:TLR8rs3764880SNP的A等位基因对男性结核病的发展具有保护性(AvsG,OR=0.58,95CI=0.37-0.91)。发现rs3764880SNP的AA基因型增加了女性的PTB风险,OR为4.81(1.11-20.85)。发现TLR9SNPrs187084的G等位基因增加PTB的风险(GvsA,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显著性。发现TLR9rs187084SNP的GA基因型增加PTB的风险,OR为1.68(1.07-2.65),但发现降低MTB感染的风险,OR=0.64(0.41-0.98)。TLR9_rs5743836SNP从数据分析中排除,因为最小等位基因频率<1%。
结论:我们在两个独立样本中的发现表明,TLR8和TLR9中的SNP与结核病的发展有关,并强调SNP可能对疾病的发病机制和进展有不同的影响。
BACKGROUND: 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.
METHODS: 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.
RESULTS: 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%.
CONCLUSIONS: 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.