Abstract
BackgroundAllergic rhinitis (AR) affects up to 80% of children with asthma and increases asthma severity. Thymic stromal lymphopoietin (TSLP) is a key mediator of allergic inflammation. The role of the TSLP gene (TSLP) in the pathogenesis of AR has not been studied.ObjectiveTo test for associations between variants in TSLP, TSLP-related genes, and AR in children with asthma.MethodsWe genotyped 15 single nucleotide polymorphisms (SNPs) in TSLP, OX40L, IL7R, and RXRα in three independent cohorts: 592 asthmatic Costa Rican children and their parents, 422 nuclear families of North American children with asthma, and 239 Swedish children with asthma. We tested for associations between these SNPs and AR. As we previously reported sex-specific effects for TSLP, we performed overall and sex-stratified analyses. We additionally performed secondary analyses for gene-by-gene interactions.ResultsAcross the three cohorts, the T allele of TSLP SNP rs1837253 was undertransmitted in boys with AR and asthma as compared to boys with asthma alone. The SNP was associated with reduced odds for AR (odds ratios ranging from 0.56 to 0.63, with corresponding Fisher's combined P value of 1.2 × 10-4). Our findings were significant after accounting for multiple comparisons. SNPs in OX40L, IL7R, and RXRα were not consistently associated with AR in children with asthma. There were nominally significant interactions between gene pairs.ConclusionsTSLP SNP rs1837253 is associated with reduced odds for AR in boys with asthma. Our findings support a role for TSLP in the pathogenesis of AR in children with asthma.
Highlights
Allergic rhinitis (AR) is a common chronic disease, affecting 10-30% of adults and 40% of children [1]
Across the three cohorts, the T allele of Thymic stromal lymphopoietin (TSLP) single nucleotide polymorphisms (SNPs) rs1837253 was undertransmitted in boys with AR and asthma as compared to boys with asthma alone
TSLP SNP rs1837253 is associated with reduced odds for AR in boys with asthma
Summary
Allergic rhinitis (AR) is a common chronic disease, affecting 10-30% of adults and 40% of children [1]. Up to 80% of children with asthma have AR [4], and treatment of comorbid AR reduces the odds of asthma-related healthcare by up to 80% [5]. The role of thymic stromal lymphopoietin (TSLP) in the pathogenesis of AR has not been extensively studied. A few in vitro and murine studies with small sample size have examined TSLP expression in allergic rhinitis (AR) [13,14,15,16]. Allergic rhinitis (AR) affects up to 80% of children with asthma and increases asthma severity. Thymic stromal lymphopoietin (TSLP) is a key mediator of allergic inflammation. The role of the TSLP gene (TSLP) in the pathogenesis of AR has not been studied
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