The Association of Genetic Variants in Toll-like Receptor 2 Subfamily With Allergy and Asthma After Hospitalization for Bronchiolitis in Infancy

Koponen, Petri; Vuononvirta, Juho; Nuolivirta, Kirsi; Helminen, Merja; He, Qiushui; Korppi, Matti

doi:10.1097/inf.0000000000000253

Cited by 34 publications

(45 citation statements)

References 25 publications

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“…We have also shown previously that early- and late-onset asthma exhibit different clinical characteristics in our study21. Our findings were also consistent with several other studies that have also found some evidence of an association between TLR6 -rs5743810 T-allele and atopic asthma9, allergic rhinitis22 and allergic sensitisation23 in children.…”

Section: Discussionsupporting

confidence: 93%

The interaction between farming/rural environment and TLR2, TLR4, TLR6 and CD14 genetic polymorphisms in relation to early- and late-onset asthma

Lau

Dharmage

Burgess

et al. 2017

Sci Rep

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Asthma phenotypes based on age-of-onset may be differently influenced by the interaction between variation in toll-like receptor (TLR)/CD14 genes and environmental microbes. We examined the associations between single-nucleotide polymorphisms (SNP) in the TLR/CD14 genes and asthma, and their interaction with proxies of microbial exposure (childhood farm exposure and childhood rural environment). Ten SNPs in four genes (TLR2, TLR4, TLR6, CD14) were genotyped for 1,116 participants from the Tasmanian Longitudinal Health Study (TAHS). Using prospectively collected information, asthma was classified as never, early- (before 13 years) or late-onset (after 13 years). Information on childhood farm exposure/childhood rural environment was collected at baseline. Those with early-onset asthma were more likely to be males, had a family history of allergy and a personal history of childhood atopy. We found significant interaction between TLR6 SNPs and childhood farm exposure. For those with childhood farm exposure, carriers of the TLR6-rs1039559 T-allele (p-interaction = 0.009) and TLR6-rs5743810 C-allele (p-interaction = 0.02) were associated with lower risk of early-onset asthma. We suggest the findings to be interpreted as hypothesis-generating as the interaction effect did not withstand correction for multiple testing. In this large, population-based longitudinal study, we found that the risk of early- and late-onset asthma is differently influenced by the interaction between childhood farming exposure and genetic variations.

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Section: Discussionsupporting

confidence: 93%

The interaction between farming/rural environment and TLR2, TLR4, TLR6 and CD14 genetic polymorphisms in relation to early- and late-onset asthma

Lau

Dharmage

Burgess

et al. 2017

Sci Rep

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“…Review articles (n=28) were also excluded. Seventeen studies were excluded because they did not meet the inclusion criteria: eight did not report genotypic frequencies in cases and/or in controls24,25,38,43,44,45,46,47; two were cross-sectional studies48,49; four were family-based studies,50,51,52,53 and 3 were abstracts 54,55,56. Twenty case-control studies were eligible for meta-analysis,19,26,27,28,29,30,31,32,33,57,58,59,60,61,62,63,64,65,66,67 one study was in Portuguese,62 and another was in Chinese 64.…”

Section: Resultsmentioning

confidence: 99%

“…The magnitude of the association of polymorphisms with asthma varies depending on genetics, demographics, environmental factors, and study methodologies. Many association studies have reported that TLR polymorphisms predispose to asthma 26,47,49,52,56,59,61,68. However, some polymorphisms might not be associated with asthma susceptibility, but rather with asthma severity, such as TLR4 polymorphisms 48,51,58.…”

Section: Discussionmentioning

confidence: 99%

“…One study with a small sample size showed that TLR6 Ser249Pro C > T contributed to asthma susceptibility,30 but a larger study on the same polymorphism reported no association in both children and adults 59. However, other studies reported that polymorphisms in TLR6 were significantly associated with asthma phenotypes 44,45,56,73. Similarly, some polymorphisms in TLR7/8 have been shown to be associated with asthma disease,29,33 whereas other polymorphisms showed no association 29.…”

Section: Discussionmentioning

confidence: 99%

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

Tizaoui

Kaabachi

Hamzaoui

et al. 2015

Allergy Asthma Immunol Res

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PurposeAsthma 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.MethodsFollowing 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.ResultsMeta-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).ConclusionsThe results showed that TLR4 Asp299Gly, TLR2 Arg753Gln, and TLR9-1237 might contribute significantly to asthma susceptibility. Future genetic association studies would consolidate these findings.

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“…TLRs 1, 2, 4, 5, 6, and 10 are located on the cell surface, whereas TLRs 3, 7, 8, and 9 are located inside the cells 9 , recognising microbial components after endocytosis. TLR1, TLR2, TLR6, and TLR10 comprise the TLR2 subfamily, and TLR1 , TLR2 , TLR6 , and TLR10 gene polymorphisms seem to play a role in susceptibility to asthma, atopic eczema, and allergic rhinitis 10–12 . TLR3 recognises double-stranded viral ribonucleic acid (RNA), and, in mice, TLR3 activation by viruses combined with allergen inhalation resulted in allergic airway disease 13 .…”

Section: Introductionmentioning

confidence: 99%

Polymorphism in the gene encoding toll-like receptor 10 may be associated with asthma after bronchiolitis

Törmänen¹,

Korppi²,

Teräsjärvi³

et al. 2017

Sci Rep

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Toll-like receptors (TLRs) recognise microbes that contribute to the severity of bronchiolitis and the subsequent risk of asthma. We evaluated whether post-bronchiolitis asthma was associated with polymorphisms in the TLR3 rs3775291, TLR4 rs4986790, TLR7 rs179008, TLR8 rs2407992, TLR9 rs187084, and TLR10 rs4129009 genes. The gene polymorphisms were studied at the age of 6.4 years (mean) in 135 children hospitalised for bronchiolitis in infancy. The outcome measure was current or previous asthma. Current asthma was more common (30%) in children with the variant AG or GG genotype in the TLR10 rs4129009 gene versus those who were homozygous for the major allele A (11%) (p = 0.03). The adjusted odds ratio (aOR) was 4.30 (95% CI 1.30–14.29). Asthma ever was more common (34.6%) in girls with the TLR7 variant AT or TT genotype versus those who were homozygous for the major allele A (12.5%) (p = 0.03). The adjusted OR was 3.93 (95% CI 1.06–14.58). Corresponding associations were not seen in boys. There were no significant associations between TLR3, TLR4, TLR8, or TLR9 polymorphisms and post-bronchiolitis asthma. Polymorphism in the TLR10 gene increases and in the TLR7 gene may increase the risk of asthma in preschool-aged children after infant bronchiolitis.

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The Association of Genetic Variants in Toll-like Receptor 2 Subfamily With Allergy and Asthma After Hospitalization for Bronchiolitis in Infancy

Abstract: In this study, we demonstrated that TLR1 rs5743618 was associated with asthma and atopic eczema during the first 6 years of life after early bronchiolitis. In addition, TLR6 rs5743810 was associated with present atopy at preschool age.

Cited by 34 publications

References 25 publications

The interaction between farming/rural environment and TLR2, TLR4, TLR6 and CD14 genetic polymorphisms in relation to early- and late-onset asthma

The interaction between farming/rural environment and TLR2, TLR4, TLR6 and CD14 genetic polymorphisms in relation to early- and late-onset asthma

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

Polymorphism in the gene encoding toll-like receptor 10 may be associated with asthma after bronchiolitis

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