Research
Thymic stromal lymphopoietin (TSLP) is associated with allergic rhinitis in children with asthma
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* Corresponding author: Supinda Bunyavanich supinda@post.harvard.edu
1 Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA
2 Division of Rheumatology, Immunology and Allergy, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA
3 Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA
4 Center for Genomic Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA
5 Harvard Medical School, Boston, Massachusetts, USA
6 Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
7 Astrid Lindgren Children's Hospital, Karolinska University Hospital, Stockholm, Sweden
8 Sachs Children's Hospital, Stockholm, Sweden
9 Department of Neurology, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts, USA
10 Pulmonary Medicine, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts, USA
11 The National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, Massachusetts, USA
12 Division of Pediatric Pulmonology, Hospital Nacional de Niños, San José, Costa Rica
13 Division of Pulmonary Medicine, Allergy, and Immunology, Children's Hospital of Pittsburgh of the University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
14 Department of Internal Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
15 Department of Human Genetics, University of Pittsburgh Graduate School of Public Health, Pittsburgh, Pennsylvania, USA
Clinical and Molecular Allergy 2011, 9:1 doi:10.1186/1476-7961-9-1
Published: 18 January 2011Abstract
Background
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.
Objective
To test for associations between variants in TSLP, TSLP-related genes, and AR in children with asthma.
Methods
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.
Results
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.
Conclusions
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.