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Meta-Analysis
. 2015 May 8:15:57.
doi: 10.1186/s12890-015-0049-4.

Association between toll-like receptors 9 (TLR9) gene polymorphism and risk of pulmonary tuberculosis: meta-analysis

Zhi Chen  1 , Wei Wang  2 , Jianqin Liang  3 , Jinhe Wang  4 , Shisheng Feng  5 , Guangyu Zhang  6
Affiliations
Meta-Analysis

Association between toll-like receptors 9 (TLR9) gene polymorphism and risk of pulmonary tuberculosis: meta-analysis

Zhi Chen et al. BMC Pulm Med. .

Abstract

Background: Previous studies indicated that the single nucleotide polymorphisms (SNPs) in TLR9 gene might be associated with Tuberculosis (TB) risk. However, the results are inconsistent and inconclusive.

Methods: 1745 articles from four databases were involved in our study. A meta-analysis on the associations between the seven polymorphisms and TB risk was carried out by comparison using different genetic models.

Results: In this systematic review 8 studies from seven English articles were analyzed. Our results showed that rs352139 is significantly associated with TB risk (AA vs. AG, OR 0.77, 95% CI 0.65-0.92, P = 0.004). In the ethnic subgroup analysis, Indonesians with AA genotype had a decreased susceptibility while Mexicans with GG allele had an increased risk.

Conclusions: The meta-analysis indicated that rs352139 polymorphism might be associated with decreased TB risk in Indonesians whereas increased risk in Mexicans. Whether the observed association was due to causal effect needs to be further studied.

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Figures

Figure 1
Figure 1
Flow chart showing the study selection procedure. CNKI: China National Knowledge Infrastructure.
Figure 2
Figure 2
The location of TLR9 SNPs and TLR9 signaling pathway. (A) Schematic representation of human chromosome 3 showing location of TLR9 gene. (B) Schematic representation of the selected single nucleotide polymorphisms (SNPs) in TLR9. Drak regions in exon 1&2: protein coding region. (C) Schematic representation of selected SNPs in TLR9 protein. TLR9: Toll-Like Receptor; LRR: Leucine-rich repeat; TIR: Toll-Interleukin-1 Receptor Domain; LD: linkage disequilibrium. (D) The signaling pathway of TLR9. TLR9 homodimer could recruit adaptor proteins MyD88. MyD88 recruits IRAK-4 and activates NF-κB through IRAKs, TRAF6, TAK1, and IκKs, resulting in cell apoptosis or inflammatory cytokine synthesis. TLR9: Toll-Like Receptor 9; MyD88: Myeloid Differentiation Primary Response Gene 88; NF-κB: nuclear factor kappa B; IRAK: Interleukin-1 Receptor associated kinase 1; TRAF 6: TNF Receptor Associated Factor 6; TAK1: TGF-b-Actiated Kinase 1; IκK: IκB kinase; IκB: Inhibitor of NF-κB.
Figure 3
Figure 3
Forrest plot of the association between rs187084 and TB risk (T vs. C). Subgroup analysis was performed by ethnicity. OR: odds ratio; CI: confidence interval; df: degrees of freedom.
Figure 4
Figure 4
Forrest plot of the association between rs5743836 and TB risk (T vs. C). Subgroup analysis was performed by ethnicity. OR: odds ratio; CI: confidence interval; df: degrees of freedom.
Figure 5
Figure 5
Forrest plot of the association between rs352139 and TB risk (AA vs. AG + GG). Subgroup analysis was performed by ethnicity. OR: odds ratio; CI: confidence interval; df: degrees of freedom.
Figure 6
Figure 6
Forrest plot of the association between rs352139 and TB risk (AA vs. AG). Subgroup analysis was performed by ethnicity. OR: odds ratio; CI: confidence interval; df: degrees of freedom.
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References

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