TSLP polymorphisms, allergen exposures, and the risk of atopic disorders in children.

BACKGROUND

Thymic stromal lymphopoietin (TSLP) polymorphisms influence atopy risk. TSLP might constitute a key interface between the environment and the allergic immune response. However, whether the effects of TSLP polymorphisms on atopic dermatitis (AD) are modified by allergic sensitization is not clear.

OBJECTIVE

To evaluate the joint effect of allergic sensitization and TSLP polymorphisms on AD and to test whether TSLP polymorphisms increase the risk of asthma in children with AD.

METHODS

A total of 1,520 kindergarten children (375 with AD and 1,145 controls) selected from the Childhood Environment and Allergic Diseases Study cohort in 2010 were enrolled. Information about allergic diseases and environmental exposures was collected by questionnaire. Skin prick tests were performed to measure allergic sensitization. TSLP polymorphisms were genotyped by TaqMan assay. Logistic regressions were conducted to estimate the association among TSLP polymorphisms, allergic sensitization, and AD. For replication, a subsample of the British Isle of Wight birth cohort was used.

RESULTS

The TSLP rs2289278 CC genotype increased the risk of AD (odds ratio 1.90, 95% confidence interval 1.12-3.22). In children sensitized to certain allergens, a genetic predisposition (rs2289278 genotype CC) significantly increased the risk of AD. These findings were replicated in the British subsample using rs2289276 genotypes TT and TC, which are in linkage disequilibrium with rs2289278. In subjects with AD, the rs2289278 C allele also significantly increased the risk of developing asthma (odds ratio 8.31, 95% confidence interval 1.08-64.13).

CONCLUSION

The association of rs2289278 with AD was stronger in children with allergic sensitization than in children without atopy. TSLP polymorphisms also increased the risk of asthma in children with AD.