Yonsei Med J.  2015 Sep;56(5):1274-1287. 10.3349/ymj.2015.56.5.1274.

IL-10 Polymorphisms and Tuberculosis Susceptibility: An Updated Meta-Analysis

• Ke Z
• Yuan L
• Ma J
• Zhang X
• Guo Y
• Xiong H

• KMID: 2163619
• DOI: http://doi.org/10.3349/ymj.2015.56.5.1274

Abstract

PURPOSE
The association of interleukin-10 (IL-10) polymorphisms (-1082G/A, -819C/T, -592A/C) and interleukin-6 (IL-6) poly-morphisms (-174G/C) with tuberculosis (TB) risk has been widely reported. However, the results are controversial. To clarify the role of these polymorphisms in TB, we performed a meta-analysis of all available and relevant published studies.
MATERIALS AND METHODS
Based on comprehensive searches of the PubMed, Medline, Embase, Web of Science, Elsevier Science Direct and Cochrane Library database, we identified outcome data from all articles estimating the association between IL-10 and IL-6 polymorphisms and TB risk.
RESULTS
The results indicated significant association of the allele model, heterozygous model and dominant model of IL-6 -174G/C polymorphism with decreased risk of TB. In the stratified analysis by ethnicity, significantly increased risk was observed for IL-10 -1082G/A polymorphism in Europeans under recessive model, for IL-10 -819C/T polymorphism in Asians under heterozygous model and dominant model and IL-10 -592A/C polymorphism in Asians under Allele model, homozygous model and recessive model. Moreover, significantly decreased risk of TB was associated with Asians for IL-6 -174C/G polymorphism in allele model, heterozygous model and dominant model. We also performed the analyses by sample types in IL-10 -1082G/A polymorphism, and observed significantly increased TB risk in mixed group under homozygous model.
CONCLUSION
The results suggested that the IL-10 -1082G/A polymorphism is associated with increased TB risk in Europeans, while IL-10 -819C/T and IL-10 -592A/C polymorphisms in Asians. However, IL-6 -174G/C polymorphism might be a genetic risk factor that decreases TB susceptibility in Asians.

Keyword

IL-10; IL-6; polymorphism; tuberculosis; susceptibility; meta-analysis

MeSH Terms

Alleles
Asian Continental Ancestry Group/genetics/statistics & numerical data
Case-Control Studies
European Continental Ancestry Group/genetics/statistics & numerical data
*Genetic Predisposition to Disease
Humans
Interleukin-10/*genetics
Interleukin-6/*genetics
Polymorphism, Genetic
*Polymorphism, Single Nucleotide
Risk Factors
Tuberculosis/*ethnology/*genetics
Interleukin-6
Interleukin-10

Figure

• 

  Fig. 1 Flow diagram for study selection.

• 

  Fig. 2 Forest plot of the overall risk of TB associated with the IL-10 -1082G/A and -819C/T polymorphism in all genetic models. Bars represent 95% CI and boxes represent OR values. The size of each box indicates the weight of the study in the pooled results. (F-J) T allele vs. C allele, TT vs. CC, TC vs. CC, TT+TC vs. CC, TT vs. TC+CC for -819C/T. TB, tuberculosis; IL-10, interleukin 10; CI, confidence interval; OR, odds ratio.

• 

  Fig. 3 Galbraith plot of IL-10 promoter polymorphism and TB risk. (A-E) The five studies1820223133 in G vs. A, three studies202231 in GG vs. AA, seven studies13182022313337 in AG vs. AA, six studies131820223133 in GG+AG vs. AA, and five studies2022273537 in GG vs. AG+AA were outliers for -1082G/A. (F and G) The one study38 in TC vs. CC and one study38 in TT+TC vs. CC for -819C/T. (H-K) The three studies262838 in A vs. C, one study38 in AA vs. CC, one study38 in AA+AC vs. CC, and two studies1738 in AA vs. AC+CC for -592A/C. TB, tuberculosis; IL-10, interleukin 10.

• 

  Fig. 4 Funnel plot for publication bias of the meta-analysis of tuberculosis risk and IL-10 polymorphisms in allele genetic model comparison. (A) IL-10 -1082G/A polymorphism. (B) IL-10 -819C/T polymorphism. (C) IL-10 -592A/C polymorphism. (D) IL-6 -174G/C polymorphism. IL-10, interleukin 10; IL-6, interleukin 6.

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