Filaggrin gene defects and risk of developing allergic sensitisation and allergic disorders: systematic review and meta-analysis

Abstract

Objective: To investigate whether filaggrin gene defects, present in up to one in 10 western Europeans and North Americans, increase the risk of developing allergic sensitisation and allergic disorders.

Design: Systematic review and meta-analysis.

Data sources: Medline, Embase, ISI Science Citation Index, BIOSIS, ISI Web of Knowledge, UK National Research Register, clinical trials.gov, the Index to Theses and Digital dissertations, and grey literature using OpenSIGLE.

Study selection: Genetic epidemiological studies (family, case-control) of the association between filaggrin gene defects and allergic sensitisation or allergic disorders.

Data extraction: Atopic eczema or dermatitis, food allergy, asthma, allergic rhinitis, and anaphylaxis, along with relevant immunological variables relating to the risk of allergic sensitisation as assessed by either positive skin prick testing or increased levels of allergen specific IgE.

Data synthesis: 24 studies were included. The odds of developing allergic sensitisation was 1.91 (95% confidence interval 1.44 to 2.54) in the family studies and 1.57 (1.20 to 2.07) in the case-control studies. The odds of developing atopic eczema was 1.99 (1.72 to 2.31) in the family studies and 4.78 (3.31 to 6.92) in the case-control studies. Three studies investigated the association between filaggrin gene mutations and allergic rhinitis in people without atopic eczema: overall odds ratio 1.78 (1.16 to 2.73). The four studies that investigated the association between filaggrin gene mutations and allergic rhinitis in people with atopic eczema reported a significant association: pooled odds ratio from case-control studies 2.84 (2.08 to 3.88). An overall odds ratio for the association between filaggrin gene mutations and asthma in people with atopic eczema was 2.79 (1.77 to 4.41) in case-control studies and 2.30 (1.66 to 3.18) in family studies. None of the studies that investigated filaggrin gene mutations and asthma in people without atopic eczema reported a significant association; overall odds ratio was 1.30 (0.7 to 2.30) in the case-control studies. The funnel plots suggested that publication bias was unlikely to be an explanation for these findings. No studies investigated the association between filaggrin gene mutations and food allergy or anaphylaxis.

Conclusions: Filaggrin gene defects increase the risk of developing allergic sensitisation, atopic eczema, and allergic rhinitis. Evidence of the relation between filaggrin gene mutations and atopic eczema was strong, with people manifesting increased severity and persistence of disease. Filaggrin gene mutations also increased the risk of asthma in people with atopic eczema. Restoring skin barrier function in filaggrin deficient people in early life may help prevent the development of sensitisation and halt the development and progression of allergic disease.

Fig 1 Selection of studies

Fig 2 Association between filaggrin combined genotype (≥1 mutation) and sensitisation in case-control and family studies and between filaggrin gene mutations R501X and 2282del4 and sensitisation in family studies

Fig 3 Association between filaggrin combined genotype (≥1 mutation), filaggrin gene mutation R501X, and filaggrin gene mutation 2282del4 and atopic dermatitis in case-control studies, including those of good and high quality and with hospital based cases, and family studies

Fig 4 Association between filaggrin combined genotype (≥1 mutation) and persistent atopic dermatitis or early onset atopic dermatitis in case-control studies and atopic dermatitis in family studies

Fig 5 Association between filaggrin combined genotype (≥1 mutations) and allergic rhinitis in people without and with atopic eczema in case-control studies and in people with atopic eczema in family studies

Fig 6 Association between filaggrin combined genotype (carriage of ≥1 mutation) and asthma in people without and with atopic dermatitis in case-control studies and with atopic dermatitis in family studies, filaggrin R501X mutation and asthma in people with atopic dermatitis in family studies, and filaggrin 2282del4 mutation and asthma in people with atopic dermatitis in family studies