pediatrics
October 2011, VOLUME128 /ISSUE Supplement 3

Filaggrin Gene Variants and Atopic Diseases in Early Childhood Assessed Longitudinally From Birth

K Bønnelykke, CB Pipper, R Tavendale, CNA Palmer, H Bisgaard. Pediatr Allergy Immunol. 2010;21(6):954961
  1. Satya D. Narisety, MD and
  2. Robert A. Wood, MD
  1. Baltimore, MD

PURPOSE OF THE STUDY.

Filaggrin coding gene (FLG) loss-of-function variants lead to skin-barrier dysfunction and have been associated with atopic dermatitis. These researchers sought to find associations between FLG variants and development of asthma, eczema, and sensitization to foods and aeroallergens in a high-risk birth cohort.

STUDY POPULATION.

A total of 411 infants born to mothers with a history of asthma were followed longitudinally for a 5-year period with follow-up visits at least every 6 months. Asthma, eczema, and sensitization to allergens were diagnosed prospectively. FLG variants were determined in 382 white infants.

METHODS.

Respiratory symptoms were recorded in daily diaries. Recurrent wheeze was defined as 5 episodes that each lasted 3 days in 6 months or daily symptoms for 4 consecutive weeks. Asthma and atopic dermatitis were diagnosed according to accepted criteria. Specific immunoglobulin E levels were determined by the ImmunoCAP test (Phadia, Uppsala, Sweden) at 1½ and 4 years of age for common food and aeroallergens. Genotyping for FLG variants R501X and 2282del4 was performed.

RESULTS.

The mutated alleles R501X and 2282del4 were present in 18 and 25 children, respectively, and 95 of 382 children developed asthma-related phenotypes. Differentiation in development of an asthma-related phenotype was present in the first 18 months (P = .02). Yearly incidences of acute severe asthma exacerbations were elevated from infancy in those with FLG variants and persisted throughout the 5 years (P = .01). Yearly point-prevalence of asthma was elevated in those with FLG variants that also persisted throughout the 5 years (P = .03). FLG variants were associated with eczema development in the first year of life. Point-prevalence of specific immunoglobulin E sensitization was not elevated in FLG variants by the age of 2 but was increased by the age of 4 (P = .0007).

CONCLUSIONS.

This study revealed that those with FLG variants developed eczema, asthma, and sensitization at higher rates than those without these variants in a high-risk birth cohort. The temporal pattern of FLG-associated atopic disease included early onset of asthma and eczema and later development of sensitization.

REVIEWER COMMENTS.

We do not have a clear understanding of the genetic and environmental factors that influence the development of atopic disease. This longitudinal birth cohort revealed that those high-risk infants with FLG variants have higher rates of atopic disease, which suggests that skin-barrier defects have a role in this process and that this process occurs very early in life.