TSLP polymorphisms are associated with asthma in a sex‐specific fashion

To cite this article: Hunninghake GM, Soto‐Quirós ME, Avila L, Kim HP, Lasky‐Su J, Rafaels N, Ruczinski I, Beaty TH, Mathias RA, Barnes KC, Wilk JB, O'Connor GT, James Gauderman W, Vora H, Baurley JW, Gilliland F, Liang C, Sylvia JS, Klanderman BJ, Sharma SS, Himes BE, Bossley CJ, Israel E, Raby BA, Bush A, Choi AM, Weiss ST, Celedón JC. TSLP polymorphisms are associated with asthma in a sex‐specific fashion. Allergy 2010; 65: 1566-1575. ABSTRACT: Background: Single nucleotide polymorphisms (SNPs) in thymic stromal lymphopoietin (TSLP) have been associated with IgE (in girls) and asthma (in general). We sought to determine whether TSLP SNPs are associated with asthma in a sex‐specific fashion. Methods: We conducted regular and sex‐stratified analyses of association between SNPs in TSLP and asthma in families of children with asthma in Costa Rica. Significant findings were replicated in whites and African‐American participants in the Childhood Asthma Management Program, in African‐Americans in the Genomic Research on Asthma in the African Diaspora study, in whites and Hispanics in the Children's Health Study, and in whites in the Framingham Heart Study (FHS). Main Results: Two SNPs in TSLP (rs1837253 and rs2289276) were significantly associated with a reduced risk of asthma in combined analyses of all cohorts (P values of 2 × 10⁻⁵ and 1 × 10⁻⁵, respectively). In a sex‐stratified analysis, the T allele of rs1837253 was significantly associated with a reduced risk of asthma in males only (P = 3 × 10⁻⁶). Alternately, the T allele of rs2289276 was significantly associated with a reduced risk of asthma in females only (P = 2 × 10⁻⁴). Findings for rs2289276 were consistent in all cohorts except the FHS. Conclusions: TSLP variants are associated with asthma in a sex‐specific fashion.