Replication of genomewide associations with allergic sensitization and allergic rhinitis

Nilsson, Daniel; Henmyr, Viktor; Halldén, Christer; Säll, Torbjörn; Kull, Inger; Wickman, Magnus; Cardell, Lars-Olaf

doi:10.1111/all.12495

Cited by 24 publications

(28 citation statements)

References 24 publications

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“…The TLR6 is located on chromosome 4p14, a region that was consistently associated with atopy in three GWAS161718. Early-onset asthma is more likely to be attributable to atopy15 and therefore it is not surprising to observe some evidence for the association between the two TLR6 SNPs and early-onset asthma but not late-onset asthma in our study.…”

Section: Discussionmentioning

confidence: 47%

“…The selection of CD14 rs2569190, rs5744455 and rs2915863 SNPs were based on their relationship with asthma or wheeze, sensitisation or hay fever12. The TLR6 rs5743810 and rs1039559 SNPs was selected because they have been shown to be associated with hay fever and sensitisation in three large GWAS studies161718. The SNPs from the TLR2 and TLR4 were selected based on the associations shown with asthma and atopy, and their effect modification by farming exposure in a previous study19.…”

mentioning

confidence: 99%

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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: Discussionmentioning

confidence: 47%

mentioning

confidence: 99%

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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“…TSLP polymorphisms have been studied in the context of respiratory [12,13,14,35,36,37] and cutaneous diseases [10,11], including NERD [9]. However, in this study only two imputed SNPs showed a nominal genetic association (rs1816678 and rs764917) with NIUA, suggesting a potential role of TSLP in NIUA, although this must be confirmed.…”

Section: Discussionmentioning

confidence: 63%

“…Several candidate gene association studies have assessed the importance of TSLP in NSAID-exacerbated respiratory disease (NERD) [9], atopic dermatitis [10] and eczema [11], as well as other allergy-related pathologies. In addition, genome-wide association studies have found single nucleotide polymorphism (SNPs) in TSLP to be associated with asthma [12], allergic rhinitis [13,14] and eosinophilic esophagitis in children [15]. …”

Section: Introductionmentioning

confidence: 99%

Genetic Variants of Thymic Stromal Lymphopoietin in Nonsteroidal Anti-Inflammatory Drug-Induced Urticaria/Angioedema

Plaza-Serón

Blanca‐López²,

Pérez‐Sánchez³

et al. 2016

Int Arch Allergy Immunol

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Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most frequent agents involved in hypersensitivity drug reactions, with NSAID-induced urticaria and/or angioedema (NIUA) being the most common entity. Mast cells are key players in NIUA and are activated by thymic stromal lymphopoietin (TSLP). This cytokine functions through recognition by its receptor, composed of IL7Rα (interleukin-7 receptor alpha) and TSLPR (TSLP receptor). These genes have been previously associated with other inflammatory diseases. Methods: We assessed the genetic association between single nucleotide polymorphisms (SNPs) in TSLP, IL7R and TSLPR and NIUA in Spanish individuals, using genotyped and imputed data. A total of 369 unrelated NIUA patients and 580 NSAID-tolerant control subjects were included, and 6 SNPs in TSLP, 6 in IL7R and 3 in TSLPR were genotyped. Further variants were imputed using Mach and the 1,000 Genomes Project (Phase 3) data. Association testing and statistical analyses were performed with Mach2dat and R. Results: A total of 139 SNPs were tested for association following quality control. Two SNPs in TSLP (rs1816678 and rs764917) showed a nominal association (p = 0.033 and 0.024, respectively) with NIUA, although these results were not statistically significant after correcting for multiple comparisons. Conclusions: Although TSLP, IL7R and TSLPR are important genes involved in the development of the inflammatory response, we found no significant genetic association with NIUA in our population for common SNPs in these genes.

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“…Similarly to IL-33, SNPs in the TSLP gene region have been associated with asthma as broad diagnosis (Hunninghake et al, 2010;Torgerson et al, 2011), but also with allergic rhinitis (Nilsson et al, 2014;Ramasamy et al, 2011), and recently with the combined asthma and hay fever phenotype (Ferreira et al, 2014), suggesting a potential role of TSLP in allergic phenotypes. SNPs in the latter gene region are both located upstream and intragenic, still allowing several functional roles in TSLP biology, including an eQTL function and a role in protein binding (Ober and Yao, 2011;Papazian et al, 2014).…”

Section: Genetic and Clinical Evidence For The Role Of Il-33 And Tslpmentioning

confidence: 99%

IL-33 and Thymic Stromal Lymphopoietin in mast cell functions

Saluja

Zoltowska

Ketelaar

et al. 2016

European Journal of Pharmacology

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Replication of genomewide associations with allergic sensitization and allergic rhinitis

Abstract: The TLR6-TLR1 locus is likely to have a central role in the development of allergic disease. The association between genetic variation in the SSTR1-MIPOL1 and TSLP-SLC25A46 loci and age at onset is the first report of age at onset effects in allergic rhinitis.

Cited by 24 publications

References 24 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

Genetic Variants of Thymic Stromal Lymphopoietin in Nonsteroidal Anti-Inflammatory Drug-Induced Urticaria/Angioedema

IL-33 and Thymic Stromal Lymphopoietin in mast cell functions

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