TY - JOUR
T1 - Thymic stromal lymphopoietin (TSLP) is associated with allergic rhinitis in children with asthma
AU - Bunyavanich, Supinda
AU - Melen, Erik
AU - Wilk, Jemma B.
AU - Granada, Mark
AU - Soto-Quiros, Manuel E.
AU - Avila, Lydiana
AU - Lasky-Su, Jessica
AU - Hunninghake, Gary M.
AU - Wickman, Magnus
AU - Pershagen, Göran
AU - O'Connor, George T.
AU - Weiss, Scott T.
AU - Celedn, Juan C.
N1 - Funding Information:
We thank all subjects for their participation in the Genetics of Asthma in Costa Rica, CAMP, and BAMSE studies. We acknowledge the CAMP investigators and research team, supported by NHLBI, for collection of CAMP Genetic Ancillary Study data. All work on data collected from the CAMP Genetic Ancillary Study was conducted at the Channing Laboratory of the Brigham and Women’s Hospital under appropriate CAMP policies and human subject’s protections. This work was supported by the National Institute of Health [Grants R37 HL66289, U01 HL075419, P01 HL083069, T32 HL007427]; the Swedish Research Council; Stockholm County Council; Centre for Allergy Research, Karolinska Institutet; Swedish Heart Lung Foundation; Swedish Fulbright Commission; Riksbankens Jubileumsfond; Erik Rönnberg Scholarship; GABRIEL contract number 018996 under Integrated Program LSH-2004-1.2.5-1; the Wellcome Trust [WT084703MA].
PY - 2011/1/18
Y1 - 2011/1/18
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=78651434663&partnerID=8YFLogxK
U2 - 10.1186/1476-7961-9-1
DO - 10.1186/1476-7961-9-1
M3 - Article
AN - SCOPUS:78651434663
SN - 1476-7961
VL - 9
JO - Clinical and Molecular Allergy
JF - Clinical and Molecular Allergy
M1 - 1
ER -