New genetic clue to peanut allergy

Scientists have discovered a gene defect that “can triple the risk of a child developing an allergy to peanuts”, BBC News has reported. The affected gene, called the filaggrin gene, is already known to play a role in other allergy-related conditions, such as some forms of eczema.

These findings come from a study that looked at how common filaggrin mutations were in 461 Europeans and Canadians with peanut allergy and in 1,891 people not known to have the condition (the control group). Up to 19% of people with peanut allergy were found to carry at least one mutated copy of the gene, compared with between about 4% and 11% of the controls.

Importantly, not all people with filaggrin mutations had peanut allergy, and not all people with peanut allergy had mutations detected in this gene. This suggests that other genes may also be involved and these may also interact with each other and the environment to determine whether a person develops a peanut allergy. The findings also need confirmation in larger groups and in samples with different ethnicities.

The discovery of this genetic link will hopefully help researchers to understand the condition better, which may lead to better treatments in the long term. However, this will take time, and is not guaranteed.

Where did the story come from?

The study was carried out by researchers from the University of Dundee and other research institutes in the UK, Ireland, Canada and the Netherlands. The participants in this study came from various cohort studies that had been funded by a number of bodies including the UK Food Standards Agency, Canadian Dermatology Foundation, the AllerGen Network of Centres of Excellence and the Canadian Allergy, Asthma, and Immunology Foundation. The research was also supported by the British Skin Foundation, National Eczema Society, Medical Research Council, the Wellcome Trust, and by donations from anonymous families affected by eczema in the Tayside region of Scotland.

One researcher was reported to have filed patents on genetic testing methods and therapy development techniques directed at the filaggrin gene examined in this study.

The study was published in the peer-reviewed Journal of Allergy and Clinical Immunology.

News sources have generally reported this study appropriately, although some have wrongly suggested that people with filaggrin mutations face a tripled risk of peanut allergy. This claim doesn’t put the risk into context or account for the relatively high prevalence of these mutations in healthy people. The Daily Express suggests that the findings could lead to screening and that new treatments “may not be far off”. However, it is not yet clear whether either of these possibilities is likely as a result of this research.

What kind of research was this?

The authors of this study cite research that has found that about 1.2% to 1.6% of preschool and school-age children in Canada, the US and the UK have peanut allergies, and that in the US the prevalence in adults is estimated to be lower, at 0.6%. The researchers also report that studies in twins have suggested that genetic factors contribute to whether a person has peanut allergy, but it is not known which specific genes are involved.

This case-control study looked at whether a specific gene, the filaggrin gene, is associated with peanut allergy. The filaggrin protein that is encoded by this gene is known to play a role in forming a barrier over the surfaces of the body. Mutations that stop the filaggrin gene from working are known to be associated with atopic dermatitis, an allergic skin condition that is one form of eczema, as well as other allergy-related conditions. Based on this, the researchers thought that mutations in filaggrin might also be associated with peanut allergy.

This type of study is often used for looking at whether a particular gene might be related to a disease or condition.

What did the research involve?

The researchers compared the filaggrin gene in people with peanut allergy (cases) and those without the condition (controls) to see if they could find any differences. Any mutations that were found more commonly in cases than controls could potentially have contributed to the development of their peanut allergy.

The researchers initially looked at 71 people with confirmed peanut allergy and 1,000 people without peanut allergy. These cases came from England, Holland and Ireland. They had their peanut allergy confirmed in a supervised test in which they were given a small amount of peanut.

The controls were drawn from a group of infants recruited at birth from the general population in England and followed up to the age of seven or older. All had tested negative during skin prick tests for peanut allergy. It was important that the cases and controls had similar ethnic backgrounds to ensure that any differences seen were more likely to be related to the peanut allergy, than ethnic differences. The researchers looked for two filaggrin mutations that are the most common among Europeans.

The researchers then carried out analyses to see whether these mutations were more common in those with peanut allergy than in controls. These analyses took into account whether people had atopic dermatitis, which is a condition associated with filaggrin mutations.

After doing this, they repeated their assessments in a second set of cases and controls. This group included 390 white Canadian patients with confirmed peanut allergy, and 891 white Canadian controls from the general population. The cases in this study had either been confirmed by peanut consumption tests (as in the European cases), clinical history of peanut allergy, skin prick test or measurement of antibodies to peanut in the blood. It was unknown whether or not the controls had peanut allergy or atopic dermatitis. The researchers looked for four filaggrin mutations that are the most common among Canadians, two of which were the same as the mutations assessed in the Europeans.

All of the mutations assessed would cause the filaggrin gene not to work.

What were the basic results?

The researchers found that 59 out of the 71 European cases (83.1%), and 963 out of 1,000 controls (96.3%) had no filaggrin mutations. A higher proportion of European cases (12 out of 71; 16.9%) than controls (37 of the 1000; 3.7%) carried at least one mutated copy of the filaggrin gene. The researchers had similar findings for the Canadian sample, where 19.2% of cases and 11.0% of controls carried at least one mutated copy of the filaggrin gene.

Statistical analyses showed that there was a strong association between the filaggrin mutations and peanut allergy in both the European and Canadian samples. This association remained after taking into account whether people had atopic dermatitis, which is associated with filaggrin mutations. Overall, a person with a peanut allergy was about 3.8 times more likely to have at least one mutated copy of the filaggrin gene than control inviduals.

How did the researchers interpret the results?

The researchers concluded that “filaggrin mutations represent a significant risk factor for IgE-mediated peanut allergy”.

Conclusion

This research has suggested that mutations in the filaggrin gene may play a role in the development of peanut allergy. The findings would need to be confirmed by other research groups in larger samples, as well as in samples with different ethnicities. Further studies will also be needed to investigate the mechanisms by which mutations in this gene might play a role in the development of peanut allergy.

Importantly, not all people with mutations in this gene were known to have peanut allergy, and most people with peanut allergy did not have the mutations in this gene that were tested for in this study. As the study only looked for four known mutations within the filaggrin gene, some people may have had other mutations in the gene that would not have been detected in this study. There may be other genes involved in this condition, and environmental factors are also likely to play a role. This also means that screening for these specific mutations would not be able to identify most people with peanut allergy, as had been suggested by some news sources. Such testing would also wrongly identify some people who did not have the allergy.

Another limitation to the study is that the Canadian controls were not assessed for the presence of peanut allergy, and it is possible that some of them had peanut allergy. Also, because the English controls were not followed up for a lifetime it is possible that some may have gone on to develop peanut allergy. However, this would tend to make any link with the filaggrin gene seem weaker than it truly was.

The discovery of this genetic link will hopefully help researchers to understand the condition better, which may eventually lead to better treatments in the long term. However, it does not immediately suggest new treatment approaches and appears to be only one piece of the puzzle.