Researchers have pinpointed a region in the human genome associated with peanut allergy in U.S. children, offering strong evidence that genes can play a role in the development of food allergies.
But in an additional finding that suggests genes are not the only players in food allergies, the Johns Hopkins Bloomberg School of Public Health-led research team found there may be other molecular mechanisms that may contribute to whether those who are genetically predisposed to peanut allergies actually develop them.
The findings are published online Feb. 24 in the journal Nature Communications.
“We always suspected it, but this is the first genome-wide association study (GWAS) that identified a genetic link to well-defined peanut allergy,” says the study’s principal investigator, Xiaobin Wang, MD, ScD, MPH, the Zanvyl Krieger Professor and Director of the Center on the Early Life Origins of Disease at the Johns Hopkins Bloomberg School of Public Health.
Food allergies have been rising rapidly in the U.S. and around the world over the past 20 years and now affect an estimated two to 10 percent of children in the United States. Food allergies have become a major clinical and public health problem due to their increasing prevalence, their potential to be life threatening and their enormous medical and economic impact. Peanut allergy is among the most fatal food allergies and is often a lifelong allergy, unlike milk or egg allergies which most children will grow out of.
There is currently no effective prevention or treatment approved by the U.S. Food and Drug Administration, except for emergency treatment given after accidental exposure. The only effective prevention strategy is to avoid the food that triggers a reaction. This can be a challenging task given the three most common allergies in American children are peanut, egg and milk, items that are widely found in processed foods.
Peanut Allergy Prevalence
- Peanut and tree nut (pecans, walnuts, almonds, etc.) allergy can be a serious condition that affects approximately three million Americans, or 1.1 percent of the population.
- Peanuts are the leading cause of severe food allergic reactions, followed by shellfish, fish, tree nuts and eggs. (Food Allergy Network)
Peanut Allergy Characteristics
Peanut allergy can be characterized by more severe symptoms, such as gastrointestinal, skin and respiratory symptoms, than other food allergies and by a high rate of symptoms on minimal contact. (“Clinical characteristics of peanut allergy,” Clin. Exp. Allergy, 1997; “An evaluation of the sensitivity of subjects with peanut allergy to very low doses of peanut protein,” J. Allergy Clin. Immunol., 1997)
Severe sufferers also may experience potentially life-threatening anaphylactic shock in response to ingestion of peanuts. Anaphylactic shock is an allergic reaction in which the release of histamine causes swelling, difficulty in breathing, heart failure, circulatory collapse, and sometimes death.
As many as one-third of peanut-sensitive patients have severe reactions, such as fatal and near-fatal anaphylaxis. (“Anaphylactic deaths in asthmatic patients,” Allergy Proc., 1989)
Avoidance of peanuts is very difficult because peanuts are commonly used as an adulterant in the preparation of foods. (Allergic reaction to inadvertent peanut contact in a child,” Allergy Asthma Proc., 1997)
In their study, Wang and her colleagues analyzed DNA samples from 2,759 participants (1,315 children and 1,444 of their biological parents) enrolled in the Chicago Food Allergy Study. Most of the children had some kind of food allergy. They scanned approximately 1 million genetic markers across the human genome, searching for clues to which genes might contribute to increased risk of developing food allergies, including peanut. They found that a genomic region harboring genes such as HLA-DB and HLA-DR and located on chromosome six is linked to peanut allergy. This study suggests that the HLA-DR and -DQ gene region probably poses significant genetic risk for peanut allergy as it accounted for about 20 percent of peanut allergy in the study population.
Not everyone with these mutations, however, develops peanut allergy, and researchers wondered why. One possible reason, they determined, was that epigenetic changes may also play a role. Epigenetic changes, in which a methyl group attaches itself to the DNA, alter the expression of a gene without altering its underlying code. The levels of DNA methylation regulate whether people with genetic susceptibility to the peanut allergy actually developed it.
While the study represents a “good first step,” more research is needed. For example, a better understanding of genetic susceptibility will allow for early risk assessment and prediction of food allergies, perhaps as early as in utero, Wang says.
The growing prevalence of peanut allergies - which have more than quadrupled in the U.S. in the 13 years ended 2010 - has puzzled and worried the medical community. More than 2% of children age 18 years and younger have a peanut allergy, according to a 2008 study. Peanut allergies are the leading cause of death related to food allergy in the U.S. and many day-care centers, schools and summer camps enforce no-peanut policies.
For years doctors advised parents of children at risk for food allergies to avoid peanuts until the child was 3 years old, based on guidelines outlined by the American Academy of Pediatrics in 2000. In 2008 the AAP revised its guidelines, citing insufficient evidence that delays prevented the development of food allergies. But the medical group didn’t say when and how highly allergenic foods should be introduced.
The new study, which was also presented Monday at the annual meeting of the American Academy of Allergy Asthma and Immunology in Houston, found that 17.2% of the children who avoided peanuts until age 5 ended up with a peanut allergy compared with 3.2% of those who regularly ate peanuts, said George Du Toit, a consultant in pediatric allergy at King’s College London and a co-investigator of the study.
The study showed consuming peanuts appeared to keep the immune system from becoming sensitized to peanut protein, known as primary allergy prevention. It also appeared to block an allergic disease from developing after the immune system had been sensitized, known as secondary prevention.
The researchers are currently working on a follow-up study to see whether the children in the peanut-consumption group would remain allergy-free if they subsequently stopped eating peanuts for an extended period. The results of that study are expected later in 2015.
While researchers believe delayed introduction to certain foods may have played a role in the increased prevalence of food allergies, there are many other possible factors. Some experts believe that as westernized countries have become more hygienic, children aren’t exposed to the same level of germs, which can affect the development of the immune system.
Some experts say it is likely that early introduction of other highly allergenic foods - such as eggs, fish and dairy products - also could help prevent allergies, but more studies are needed.
Unlike genes themselves, DNA methylation levels can change in response to environmental exposures, (in particular, in-utero and during the first few years of life) and the changes are potentially reversible. By identifying what environmental factors can alter DNA methylation levels in people with genes that make them susceptible to peanut allergy, researchers could potentially open a new avenue for prevention and treatment of peanut allergy.
“Hopefully, one day, we can manage or prevent food allergies in a safe, simple, effective way,” Wang says. “We might be able to use pharmaceutical treatment, but if we can figure out whether a lifestyle, nutrition or environmental change could reduce allergies, that would be even better.”
“One in 13 children in the U.S. have food allergies, and peanut is the most common food allergen among children,” says James R. Baker, Jr., MD, CEO of FARE. “This important study adds critical insights that will help us understand the rise in the prevalence of peanut allergy, and we look forward to further exploration of these findings.”
“Genome-wide association study identifies peanut-allergy specific loci and evidence of epigenetic mediation in U.S. children” was written by Xiumei Hong, Ke Hao, Christine Ladd-Acosta, Kasper D. Hansen, Hui-Ju Tsai, Xin Liu, Xin Xu, Timothy A. Thornton, Deanna Caruso, Corinne A. Keet, Yifei Sun, Guoying Wang, Wei Luo, Rajesh Kumar, Ramsay Fuleihan, Anne Marie Singh, Jennifer S. Kim, Rachel E. Story, Ruchi Gupta, Peisong Gao, Zhu Chen, Shelia O. Walker, Tami R. Bartell, Terri H. Beaty, M. Daniele Fallin, Robert Schleimer, Patrick G. Holt, Kari Christine Nadeau, Robert A. Wood, Jacqueline A. Pongracic, Daniel E. Weeks and Xiaobin Wang.
This research was supported by grants from the Bunning Family and their family foundations, Food Allergy Research & Education (FARE) and the National Institute of Allergy and Infectious Diseases (U01 AI090727, R56AI080627 and R21AI088609).
Johns Hopkins University Bloomberg School of Public Health