Thymic stromal lymphopoietin (TSLP) is associated with allergic rhinitis in children with asthma

To test for associations between variants in TSLP, TSLP-related genes, and AR in children with asthma.We 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.Across 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.TSLP 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.Allergic rhinitis (AR) is a common chronic disease, affecting 10-30% of adults and 40% of children [1]. Characterized by nasal congestion, itching, rhinorrhea, and sneezing, AR decreases school and work productivity. AR is a risk factor for asthma exacerbations and asthma-related hospitalization [2,3]. 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]. A better understanding of the pathophysiology of AR could decrease morbidity in asthmatics and in children overall.The role of thymic stromal lymphopoietin (TSLP) in the pathogenesis of AR has not been extensively studied. TSLP is an interleukin (IL)-7