Allergy Asthma Immunol Res.  2015 Mar;7(2):130-140. 10.4168/aair.2015.7.2.130.

Association of Single Nucleotide Polymorphisms in Toll-like Receptor Genes With Asthma Risk: a Systematic Review and Meta-analysis

• Tizaoui K
• Kaabachi W
• Hamzaoui K
• Hamzaoui A

• KMID: 2365541
• DOI: http://doi.org/10.4168/aair.2015.7.2.130

Abstract

PURPOSE
Asthma is a complex disease, with contributions from multiple genes, various genetic backgrounds, and environmental factors. Many human epidemiological studies have demonstrated that single nucleotide polymorphisms (SNPs) in Toll-like receptor (TLR) genes are inconsistently associated with asthma risk. Some have demonstrated differences concerning the study design and effect size, and conflicting results have been reported. A meta-analysis is necessary to determine the magnitude of this association.
METHODS
Following the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines, a systematic search and meta-analysis of the literature was conducted to estimate the association of SNPs in TLR genes with asthma risk. We screened the medical literature based on the following keyword searches in MEDLINE and EMBASE databases: 'TLR', 'polymorphism', 'asthma', and their combinations.
RESULTS
Meta-analysis of eight studies on TLR4 Asp299Gly showed a marginal association of TLR4 with asthma risk (odds ratio [OR]=0.814 [95% confidence interval [CI], 0.652-1.016; P=0.069]) in the recessive model. TLR4 Thr399Ile was not associated with asthma risk under any genetic model. Meta-analysis of four studies on TLR2 Arg753Gln indicated that TLR2 might be significantly associated with asthma in the dominant and codominant models (P=0.029, P=0.030, and P=0.009, respectively). TLR9 -1237 was marginally associated with asthma risk (OR=0.408 [95% CI, 0.163-1.021; P=0.065]) in the codominant model. Analysis using the allele contrast model showed that the major TLR9 -1237 T allele tended to be a significant protective factor with OR=0.689 (95% CI, 0.471-1.007; P=0.055).
CONCLUSIONS
The results showed that TLR4 Asp299Gly, TLR2 Arg753Gln, and TLR9-1237 might contribute significantly to asthma susceptibility. Future genetic association studies would consolidate these findings.

Keyword

Asthma; TLR genes; SNPs; association; meta-analysis

MeSH Terms

Alleles
Asthma*
Genetic Association Studies
Humans
Models, Genetic
Polymorphism, Single Nucleotide*
Toll-Like Receptors*
Toll-Like Receptors

Figure

• 

  Fig. 1 Flow diagram of the systematic review and meta-analysis literature search results.

• 

  Fig. 2 Forest plot of the association between TLR4 Asp299Gly and asthma risk: AA vs AG+GG. The forest plot shows the odds ratios (ORs) and respective 95% confidence intervals (CIs) for the studies included in the meta-analysis. For each study in the forest plot, the area of the black square is proportional to the study weight, and the horizontal bar represents the 95% CI. Z score: the standardized expression of a value in terms of its relative position in the full distribution of values.

• 

  Fig. 3 Forest plot of the association between TLR4 Thr399Ile and asthma risk: C allele vs T allele. The forest plot shows the ORs and respective 95% CIs for the studies included in the meta-analysis. For each study in the forest plot, the area of the black square is proportional to the study weight, and the horizontal bar represents the 95% CI. Z score: the standardized expression of a value in terms of its relative position in the full distribution of values.

• 

  Fig. 4 Forest plot of the association between TLR2 Arg753Gln and asthma: GG+AA vs GA. The forest plot shows the ORs and respective 95% CIs for the studies included in the meta-analysis. For each study in the forest plot, the area of the black square is proportional to the study weight, and the horizontal bar represents the 95% CI. Z score: the standardized expression of a value in terms of its relative position in the full distribution of values.

• 

  Fig. 5 Forest plot of the association between TLR9 -1237 and asthma: T allele vs C allele. The forest plot shows the (ORs and respective 95% CIs for the studies included in the meta-analysis. For each study in the forest plot, the area of the black square is proportional to the study weight, and the horizontal bar represents the 95% CI. Z score: the standardized expression of a value in terms of its relative position in the full distribution of values.

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