Filaggrin polymorphism P478S, IgE level, and atopic phenotypes

Background: Whether environmental exposures may modulate the effect of the skin barrier gene on atopic dermatitis (AD) remains to be elucidated. Objectives: To determine whether filaggrin (FLG) variants can serve as a predictor for atopic disorders in Chinese individuals and if allergen exposures may modify the effect of FLG variants on AD by total IgE levels. Methods: In total, 116 children aged 2-5 years with AD and 212 control subjects were analysed for the FLG variants using DNA sequencing. Multiple logistic regression models were performed to estimate the association among FLG polymorphisms and atopic phenotypes. Serum total IgE level, standing for the degree of allergen exposures, was later stratified to determine the effects of FLG polymorphisms on AD. Results: A significant difference in genotype frequency was found among AD cases and controls in FLG P478S polymorphism. FLG P478S GG genotype significantly increased the risk of AD [odds ratio (OR) 4.60, 95% confidence interval (CI) 1.88-11.24]. In addition, among subjects with AD, GG genotypes also significantly increased the risk of developing asthma (OR 4.68, 95% CI 1.37-16.03). Further, a similar result was obtained for allergic rhinitis (OR 3.23, 95% CI 1.01-10.30). Interestingly, the P478S GG genotype was significantly related to AD (OR 5.67, 95% CI 1.93-16.60) in children with IgE level ≥ 100 kU L^-1. However, the association was not evident when IgE level was <100 kU L^-1. Conclusions: Our results suggest that the FLG P478S polymorphism may confer susceptibility to the development of AD among Chinese individuals and may be modified by IgE levels.