Department of Laboratory Medicine, Chengdu Second People's Hospital, Chengdu 610017, PR China.
Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu 610041, PR China.
Infect Genet Evol. 2018 Jun;60:173-180. doi: 10.1016/j.meegid.2018.02.031. Epub 2018 Feb 24.
Abundant studies have suggested that TLR2 genetic variants involve in susceptibility to TB infection. We tried to verified the hypothesis that TLR2 genetic loci effect on the susceptibility to TB in the Western Chinese population.
A total 1109 individuals (634 TB patients and 475 healthy controls) were genotyped for rs3804099, rs3804100 and rs76112010 by using a custom-by-design 2x48-Plex SNP scan TM Kit. The statistical analysis between candidate 3 SNPs and risk and phenotypes of TB were conducted in this study. Significant SNPs were further interrogated in relation to TB susceptibility to TB infection and clinical phenotypes.
None of the three genetic loci (rs3804099, rs3804100 and rs76112010) showed statistically significant differences between all TB cases and healthy controls in genotype, allele frequencies and genetic models (all p > 0.05). Statistical comparisons of retreatment TB cases and healthy controls or primary cases revealed that rs3804099 was significantly associated with the increased risk of developing TB in Western Chinese population. For genotypes frequencies, the subgroups of retreatment TB group versus healthy control group analysis and retreatment TB group versus primary TB group analysis results showed the p = 0.041 and p = 0.002 respectively. For recessive model, the subgroup of retreatment TB group versus healthy control group and retreatment TB group versus primary TB group analyses showed the p = 0.028 and P = 0.002 after Bonferroni correction respectively. Furthermore, analysis of the genotypes of rs76112010 in relation to clinical phenotypes of active TB using the dominant model demonstrated that it was strongly correlated with different hematological parameters (Erythrocyte P = 0.043, Hemoglobin P = 0.047, Hematocrit P = 0.027).
Our study presented the significant associations of rs3804099 with TB susceptibility in the retreatment TB subgroup analysis. Our study proposed that common TLR2 genetic variants may influence TB development and disease phenotypes in Western Chinese population.
大量研究表明 TLR2 基因变异与结核感染易感性有关。我们试图验证 TLR2 基因座对中国西部地区人群结核易感性的影响假设。
采用定制的 2x48-Plex SNP 扫描 TM 试剂盒，对 1109 名个体（634 名结核患者和 475 名健康对照者）进行 rs3804099、rs3804100 和 rs76112010 的基因分型。本研究对候选 3 个 SNP 与结核的风险和表型之间的关系进行了统计分析。对显著的 SNP 进行了进一步的分析，以了解它们与结核感染和临床表型的关系。
在所有结核病例和健康对照组的基因型、等位基因频率和遗传模型中，三个遗传位点（rs3804099、rs3804100 和 rs76112010）均无统计学显著差异（均 P>0.05）。对复治性结核病例和健康对照组或初治性病例的统计学比较显示，rs3804099 与中国西部地区人群结核发病风险增加显著相关。在基因型频率方面，复治性结核组与健康对照组亚组分析和复治性结核组与初治性结核组亚组分析结果分别为 P=0.041 和 P=0.002。在隐性模型中，复治性结核组与健康对照组和复治性结核组与初治性结核组亚组分析的 P 值分别为 0.028 和 P=0.002，经过 Bonferroni 校正。此外，采用显性模型对 rs76112010 的基因型与活动性结核的临床表型进行分析表明，它与不同的血液学参数有很强的相关性（红细胞 P=0.043，血红蛋白 P=0.047，血细胞比容 P=0.027）。
本研究在复治性结核亚组分析中发现 rs3804099 与结核易感性有显著关联。本研究表明，常见的 TLR2 基因变异可能影响中国西部地区人群的结核发病和疾病表型。
