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

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.

Figure 1

The data in the upper portion of the figure represents the results of genetic association between asthma and single nucleotide polymorphisms (SNPs) in TSLP genotyped in Costa Rica (in red), Childhood Asthma Management Program (CAMP-in light green for white subjects, in dark green for African-American subjects), the Children’s Health Study (CHS-in pink), the Genome Research on the African-American Diaspora (GRAAD-in light blue), and in the Framingham Heart Study (FHS-in yellow). The combined p values are represented in blue for all subjects for rs1837253 and rs2289276. For SNP rs1837253 and rs2289276 the colored symbols “o” represent all subjects, “♂” represents male subjects, and “♀” represents female subjects. The gray horizontal bar represents a nominal significance level (p value 0.05) and the red horizontal bar represents a p value of 0.05 after adjustment for multiple comparisons (p value 0.0023). The bottom portion of the figure represents the pairwise (r²) linkage disequilibrium (LD) patterns for the genotyped region in CEPH (Centre d’etude du polymorphisme humain), Costa Rican parents.