title: 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).
  
  
  CONCLUSIONS
  Mite sensitization and the FLG TT genotype couldt be associated with the development of atopic march.
authors.affiliation: Department of Pediatrics, Taipei Hospital, Ministry of Health and Welfare; College of Medicine, National Yang-Ming University; China Medical University, Taipei, Taiwan. Electronic address: wij636@gmail.com.
authors.forename: I-Jen
authors.initials: IJ
authors.lastname: Wang
authors.affiliation: Graduate Institute of Injury Prevention and Control, Taipei Medical University, Wan Fang Hospital, Taipei, Taiwan.
authors.forename: Tien-Jen
authors.initials: TJ
authors.lastname: Lin
mesh_terms: D001249:Asthma / Q000453:epidemiology* / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D003876:Dermatitis, Atopic / Q000453:epidemiology* / Q000235:genetics; D018450:Disease Progression; D004781:Environmental Exposure / Q000009:adverse effects; D005260:Female; D000091344:Filaggrin Proteins; D005500:Follow-Up Studies; D059647:Gene-Environment Interaction; D056726:Genetic Association Studies; D006801:Humans; D007381:Intermediate Filament Proteins / Q000235:genetics*; D008297:Male; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D012307:Risk Factors; D013624:Taiwan
chemical_list: C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D007381:Intermediate Filament Proteins