Brown SJ, Asai Y, Cordell HJ et al.Loss-of-function variants in the filaggrin gene are a significant risk factor for peanut allergy. J Aller Clin Immunol 127:661-667

Epithelial Genetics Group, Division of Molecular Medicine, University of Dundee, Dundee, United Kingdom.
The Journal of allergy and clinical immunology (Impact Factor: 11.48). 03/2011; 127(3):661-7. DOI: 10.1016/j.jaci.2011.01.031
Source: PubMed


IgE-mediated peanut allergy is a complex trait with strong heritability, but its genetic basis is currently unknown. Loss-of-function mutations within the filaggrin gene are associated with atopic dermatitis and other atopic diseases; therefore, filaggrin is a candidate gene in the etiology of peanut allergy.
To investigate the association between filaggrin loss-of-function mutations and peanut allergy.
Case-control study of 71 English, Dutch, and Irish oral food challenge-positive patients with peanut allergy and 1000 non peanut-sensitized English population controls. Replication was tested in 390 white Canadian patients with peanut allergy (defined by food challenge, or clinical history and skin prick test wheal to peanut ≥ 8 mm and/or peanut-specific IgE ≥ 15 kUL(-1)) and 891 white Canadian population controls. The most prevalent filaggrin loss-of-function mutations were assayed in each population: R501X and 2282del4 in the Europeans, and R501X, 2282del4, R2447X, and S3247X in the Canadians. The Fisher exact test and logistic regression were used to test for association; covariate analysis controlled for coexistent atopic dermatitis.
Filaggrin loss-of-function mutations showed a strong and significant association with peanut allergy in the food challenge-positive patients (P = 3.0 × 10(-6); odds ratio, 5.3; 95% CI, 2.8-10.2), and this association was replicated in the Canadian study (P = 5.4 × 10(-5); odds ratio, 1.9; 95% CI, 1.4-2.6). The association of filaggrin mutations with peanut allergy remains significant (P = .0008) after controlling for coexistent atopic dermatitis.
Filaggrin mutations represent a significant risk factor for IgE-mediated peanut allergy, indicating a role for epithelial barrier dysfunction in the pathogenesis of this disease.

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    • "It has also been observed that their presence increases the probability of inhalatory allergy [17], contact allergy (e.g. to nickel) [18], and allergies caused by food allergens (e.g. peanut allergens) [19]. "
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    ABSTRACT: The results of long-term epidemiological studies show that the number of people suffering from allergic diseases, especially from food allergies and atopic dermatitis (AD), is still increasing. Although the research thus far has been conducted mainly in Europe, North America, and Asia, there are also data appearing from the first studies in that field among the African population. This may indicate the importance of the problem of allergic diseases. The discovery that loss-of-function mutations in the gene coding filaggrin (FLG) are the cause of ichthyosis vulgaris marked a significant breakthrough in understanding the pathogenesis of allergic diseases. The presence of mutations in the filaggrin gene is also an important factor that predisposes to such allergic diseases as: allergic rhinitis, atopic dermatitis, atopic asthma, and food allergy. So far, over 40 loss-of-function mutations and numerous silent mutations in filaggrin have been discovered.
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    • "Previous diseases or co-morbidity are important in this respect, and it is essential to study the conditions by which an early IgE-sensitization to a food allergen develops into clinical food allergy. Allergic diseases have a strong genetic component, and recent findings that the filaggrin mutation may be a risk factor for the development of peanut allergy [6] marks a significant step toward understanding the full picture of the etiology of allergy. The apparent increase in food allergy prevalence during the last decades also calls for studies of the epigenetic regulation of the sensitization phase, a field which has not been studied so far in detail. "
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    • "As peanut sensitization is strongly related to loss-of-function variations in the filaggrin gene found in eczema [10] and to asthma [11], the relationship between peanut sensitization and peanut allergy may be confounded by eczema and asthma. To our knowledge, this has never been studied to date. "
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