Genetic Risk Factor for Peanut Allergies Identified

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It is difficult to find a school, camp or other facility catering to children these days that is not nut free. The prevalence of peanut allergies in preschool and school age children in the UK, the US and Canada is between 1.2 – 1.6%, which is about twice the rate at which it occurs in adults in these countries. Nut allergies, especially peanut allergies, are scary. And although they have been on the rise, no one really knows why. Researchers in Scotland recently reported in The Journal of Allergy and Clinical Immunology that mutations in the gene for filaggrin, a protein found in skin, are a “significant risk factor for peanut allergy” [1].

It has long been known that peanut allergies are heritable, but the gene responsible for this heritability was unknown. Filaggrin is a protein that is expressed primarily in the skin, where it binds to keratin and plays an important role in forming the protective and impenetrable barrier that makes skin such a vital organ. Mutations in the filaggrin gene have already been identified as risk factors for eczma, asthma and other allergies, which is what prompted Drs. Sara Brown at the University of Dundee in the UK and Yuka Asai at McGill University Health Centre in Montreal, Quebec, Canada, and colleagues to consider it as a candidate gene for peanut allergies.

The researchers analyzed blood or saliva from 71 white English, Dutch, and Irish people known to have peanut allergies based on an oral challenge and 1000 healthy English controls. To confirm their results, they repeated the study with 390 white Canadians who had peanut allergies and 891 white Canadian healthy controls. They looked for loss-of-function mutations — those that completely inactivate the protein — in the filaggrin gene (FLG) that are most prevalent in the European population. They found that these mutations are “strongly and significantly associated with peanut allergy.” Twenty percent of the people with peanut allergies harbored a loss-of-function mutation in the filaggrin gene in both the European and Canadian populations, compared to 5 – 10% of the control populations.

It is still unclear how nonfunctional filaggrin might allow peanut allergies to arise. Eczma is a hypersensitivity reaction in the skin that results in inflammation, and is thus very much like an allergy. It has been suggested that impairment of the epidermal barrier — as would occur if filaggrin function is disrupted — could allow allergens to penetrate into the body, causing a local inflammatory response like eczma as well as a more systemic response like asthma. Studies performed in mouse models support this hypothesis. This explains tactile peanut allergies, and to make the story even neater, eczma is a known risk factor for peanut allergies. In fact, eczma is a stronger risk factor than these loss-of-function mutations in the filaggrin gene. As for oral exposure to peanuts, some patients with eczma have increase intestinal permeability … but it is not yet known if filaggrin plays a role here. Filaggrin has not been found in the gastrointestinal tract, but it is present in the oral mucosa and possibly as far down as the esophagus.

The authors suggest that these mutations might be associated with other food allergies. As the “most significant genetic risk for peanut allergy that has been identified to date,” looking into that possibility certainly seems warranted.

Researchers at the North Carolina Agricultural and Technical State University have recently developed an enzymatic treatment that reduces two of the most potent peanut allergens in roasted peanut kernels, Ara h 1 and Ara h 2 [2]. Ninety percent of those with peanut allergies react to these two proteins. Jainmei Yu, who has been working on developing hypo-allergenic peanuts since 2005, plans to begin clinical trials as a first step of getting them. Hopefully they will be successful, and peanut butter and jelly sandwiches will become a school lunchroom staple once again.

References

1. Brown et al. Loss-of-function variants in the filaggrin gene are a significant risk factor for peanut allergy. J Allergy Clin Immunol. 2011 Mar;127(3):661-7.
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2. Yua et al. Enzymatic treatment of peanut kernels to reduce allergen levels. Food Chemistry. 2011 Aug;127(3):1014-22.