Filaggrin null mutations and childhood atopic eczema: a population-based case-control study

J Allergy Clin Immunol. 2008 Apr;121(4):940-46.e3. doi: 10.1016/j.jaci.2008.01.013. Epub 2008 Mar 4.


Background: Null mutations within the filaggrin gene (FLG) are associated with moderate-to-severe atopic eczema; their role in mild-to-moderate eczema in the general population is unknown.

Objective: We sought to investigate the significance of 5 common FLG null mutations in childhood atopic eczema in an unselected population cohort.

Methods: Eight hundred eleven English children aged 7 to 9 years were screened for FLG mutations. Eczema cases were defined by using United Kingdom diagnostic criteria and skin examination. Asthma and seasonal rhinitis cases were defined by parental questionnaire. Association between phenotype and genotype was investigated using Fisher exact test and logistic regression analysis.

Results: The 12-month period prevalence of atopic eczema was 24.2% (95% CI, 21.2% to 27.2%), with 96% (115/120) of cases having mild-to-moderate disease. The combined null genotype (carriage of > or = 1 FLG mutations) was significantly associated with atopic eczema (P = 1.2 x 10(-4)). The odds ratio (OR) for individuals carrying 2 null mutations was 26.9 (95% CI, 3.3-217.1), but heterozygote carriers showed no significant increase in risk (OR, 1.2; 95% CI, 0.7-1.9). Eight of 190 eczema cases (4.2%) carried 2 FLG null mutations and thus might be attributed to filaggrin deficiency. Asthma in the context of eczema showed significant association with the FLG null mutations (P = 7.1 x 10(-4)). There was no association of FLG with asthma independent of eczema (P = .15) and no association with seasonal rhinitis (P = .66).

Conclusion: FLG null mutations are significantly associated with mild-to-moderate atopic eczema in childhood, with a recessive pattern of inheritance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Asthma / diagnosis
  • Asthma / genetics
  • Asthma / immunology
  • Case-Control Studies
  • Child
  • Cohort Studies
  • Eczema / diagnosis
  • Eczema / genetics*
  • Eczema / immunology
  • Female
  • Genes, Recessive / immunology
  • Genetic Carrier Screening
  • Humans
  • Hypersensitivity, Immediate / diagnosis
  • Hypersensitivity, Immediate / genetics*
  • Hypersensitivity, Immediate / immunology
  • Intermediate Filament Proteins / deficiency*
  • Intermediate Filament Proteins / genetics*
  • Intermediate Filament Proteins / physiology
  • Male
  • Mutation*
  • Rhinitis, Allergic, Seasonal / diagnosis
  • Rhinitis, Allergic, Seasonal / genetics
  • Rhinitis, Allergic, Seasonal / immunology
  • Surveys and Questionnaires


  • Intermediate Filament Proteins
  • filaggrin