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Association of TLR8 and TLR9 Polymorphism with Tuberculosis Among Chinese Han Population
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A4307 - Association of TLR8 and TLR9 Polymorphism with Tuberculosis Among Chinese Han Population
Author Block: M. Wang, J. He, He Jianqing Group; Respiratory and Critical Care Medicine, West China Hospital, Chengdu, China.
Abstract Objective: Toll-like receptor’s (TLRs) polymorphisms have been associated with regulation of TLR expression and development of active tuberculosis(TB). The Objectives of this study were to determine the TLR8 and TLR9 polymorphism in Chinese Han tuberculosis patients and to investigate the role of these SNPs in the process of tuberculosis infection and the subsequent pulmonary tuberculosis (PTB). Methods: Two independent samples were undertaken in this study: discovery group contains 584 TB cases and 608 controls, and differentiation group contains 408 healthy controls (HC) without Mycobacterium tuberculosis infection, 402 latent tuberculosis infection (LTBI) patients and 209 PTB patients. 4-5 ml venous blood samples were collected from each subject in this study. Tag-SNPs (rs3764880 for TLR8, rs187084 and rs5743836 for TLR9) were genotyped using custom-by-design 2x48-Plex SNP scan TM Kit. Logistic regression method in each model (dominant, recessive, and additive) was applied to analyze genetic data. Results: In the discovery group, we found a significant association of the A allele of rs3764880 (recessive: OR= 0.712, 95% CI= 0.514-0.985, P = 0.040; additive: OR = 0.811, 95% CI = 0.685-0.961, P = 0.016) with TB after adjustment by age, gender and smoking. When comparing LTBI patients with HC in the differentiation group, we found the G allele of the rs187084 polymorphism had a protect effect on LTBI under the dominant model (OR=0.658, 95% CI= 0.441-0.982, P= 0.04). Significant associations were observed for both rs3764880 (recessive: OR= 1.727, 95% CI=1.045- 2.855, P = 0.033; additive: OR = 1.378, 95% CI= 1.065- 1.783, P = 0.015) and rs187084 (dominant: OR= 1.533, 95% CI=1.088- 2.159, P = 0.015; additive: OR = 1.336, 95% CI= 1.055- 1.692, P = 0.016) when compared PTB with LTBI. Separating test for gender of rs3764880 also showed association with developing disease with PTB in males. Conclusions: Our findings in the two independent groups indicated that the polymorphisms in TLR8 and TLR9 were associated with susceptibility to TB, and highlight that polymorphisms may have differ effects on tuberculosis infection and active pulmonary tuberculosis.
Author Block: M. Wang, J. He, He Jianqing Group; Respiratory and Critical Care Medicine, West China Hospital, Chengdu, China.
Abstract Objective: Toll-like receptor’s (TLRs) polymorphisms have been associated with regulation of TLR expression and development of active tuberculosis(TB). The Objectives of this study were to determine the TLR8 and TLR9 polymorphism in Chinese Han tuberculosis patients and to investigate the role of these SNPs in the process of tuberculosis infection and the subsequent pulmonary tuberculosis (PTB). Methods: Two independent samples were undertaken in this study: discovery group contains 584 TB cases and 608 controls, and differentiation group contains 408 healthy controls (HC) without Mycobacterium tuberculosis infection, 402 latent tuberculosis infection (LTBI) patients and 209 PTB patients. 4-5 ml venous blood samples were collected from each subject in this study. Tag-SNPs (rs3764880 for TLR8, rs187084 and rs5743836 for TLR9) were genotyped using custom-by-design 2x48-Plex SNP scan TM Kit. Logistic regression method in each model (dominant, recessive, and additive) was applied to analyze genetic data. Results: In the discovery group, we found a significant association of the A allele of rs3764880 (recessive: OR= 0.712, 95% CI= 0.514-0.985, P = 0.040; additive: OR = 0.811, 95% CI = 0.685-0.961, P = 0.016) with TB after adjustment by age, gender and smoking. When comparing LTBI patients with HC in the differentiation group, we found the G allele of the rs187084 polymorphism had a protect effect on LTBI under the dominant model (OR=0.658, 95% CI= 0.441-0.982, P= 0.04). Significant associations were observed for both rs3764880 (recessive: OR= 1.727, 95% CI=1.045- 2.855, P = 0.033; additive: OR = 1.378, 95% CI= 1.065- 1.783, P = 0.015) and rs187084 (dominant: OR= 1.533, 95% CI=1.088- 2.159, P = 0.015; additive: OR = 1.336, 95% CI= 1.055- 1.692, P = 0.016) when compared PTB with LTBI. Separating test for gender of rs3764880 also showed association with developing disease with PTB in males. Conclusions: Our findings in the two independent groups indicated that the polymorphisms in TLR8 and TLR9 were associated with susceptibility to TB, and highlight that polymorphisms may have differ effects on tuberculosis infection and active pulmonary tuberculosis.
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