Molecular Anthropology: "Loss-of-function variants in the Filaggrin gene are a significant risk factor for peanut allergy"

One of the most common food allergies seen in the US population today is peanuts. Unlike many food allergies, a peanut allergy is not one that can be outgrown—it is lifelong. Within the past three decades, pediatricians have witnessed an increase in the number of patients born with peanut allergies. This is not solely an American phenomenon—similar trends have been noted in populations throughout the world.

Researchers have long hypothesized that there might be a genetic basis for the peanut allergy. Several facts support this hypothesis: as previously mentioned, peanut allergy is a lifelong disease. Additionally, the disease appears to be inheritable. Until this past spring, though, no known genetic link had been found between a patient’s genotype and their risk for having a peanut allergy.

That unknown link was unearthed in March of 2011, when a University of Dundee-led research team discovered a link between mutations of the Filaggrin gene and likelihood of having a peanut allergy. Published in the Journal of Allergy and Clinical Immunology, the study aimed to pinpoint a specific gene that could be linked to peanut allergies. They focused on the gene Filaggrin, that (when functioning properly) codes for a protein of the same name that makes skin an effective barrier against irritations and allergens. [See photo for structure of Filaggrin gene.] However, mutations in the gene can cause loss of function, and were previously associated with atopic diseases (when a hypersensitivity reaction occurs in a part of the body not in contact with the allergen), such as asthma and eczema. Scientists this spring wanted to see whether it might too be associated with another atopic disease, peanut allergies.

Researchers used a test pool of 71 children—all of whom were known to be allergic to peanuts—in order to try to determine whether mutations in the Filaggrin gene could be a factor in the disease. The patients were from England, Ireland, and the Netherlands. Scientists found that 1 in 5 of the patients had a mutation of the Filaggrin gene, whereas patients in a control group (who were known to be allergy-free) did not. Most importantly, the general results of this study were confirmed in a similar study in Canada, which had a much larger test pool of 390 patients with allergies, and a control group of 1000 patients.

Several implications can be drawn from the results of this study. For the first time, a genetic link was established with the peanut allergy, across multiple geographic populations. Researchers concluded that the Filaggrin mutation was in fact “strongly and significantly associated,” and “firmly linked,” with peanut allergies. While it is not the sole cause of peanut allergies, it is the “single most significant genetic risk” factor found to date. Finally, the study may even underestimate its significance as a factor, because the study only focused on the most common mutations of Filaggrin, but there may be others that play a role.