FLG P478S polymorphisms and environmental risk factors for the atopic march in Taiwanese children: a prospective cohort study.

ABSTRACT

BACKGROUND: Little is known about the role of genetic and environmental modifiers in atopic march. OBJECTIVE: To investigate the effects of filaggrin (FLG) P478S polymorphisms and environmental factors on the risk of asthma in a cohort of children with atopic dermatitis (AD). METHODS: In 2010, 3,246 children from Childhood Environment and Allergic Diseases Cohort Study cohort were recruited. There were 485 children with AD who were invited for further clinical evaluation. Environmental exposures and skin prick tests for allergens were collected at 3 years of age and the development of asthma was determined at 6 years. Multivariate logistic regressions were performed to estimate the association between genetic and environmental factors and the development asthma in children with AD. RESULTS: Of 397 children with AD who completed the follow-up, 97 developed asthma. After controlling for potential confounders, only mite sensitizations (odds ratio 1.89, 95% confidence interval 1.10-3.25) and the FLG TT genotype (odds ratio 2.26, 95% confidence interval 1.33-3.84) were significantly associated with the development of asthma in children with AD. Mite sensitizations and FLG variants had a synergistic effect on the development of asthma. When children with FLG variants were exposed to mite, the risk for asthma was compounded compared with those with FLG variants without mite exposure (odds ratio 3.58, 95% confidence interval 1.81-7.08). CONCLUSION: Mite sensitization and the FLG TT genotype couldt be associated with the development of atopic march.