Tracing Peanut Allergy’s Genetic Marks, Epigenetic Shades

The genetic risk factors for peanut allergy are a little less sketchy now that a genome-wide association study has determined that a particular gene region is likely in the picture. This region, which is located on chromosome 6, harbors genes such as HLA-DB and HLA-DR, and it appears to account for about 20% of peanut allergy. Although this effect is considerable, the consequences of the genetic features outlined in the study may not always be so dark. Rather, some lightening, shades of gray, may emerge due to epigenetic factors.

These findings appeared February 24 in Nature Communications, in an article entitled, “Genome-wide association study identifies peanut allergy-specific loci and evidence of epigenetic mediation in U.S. children.” The article describes how researchers based at Johns Hopkins University 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.

The researchers, led by principal investigator, Xiaobin Wang, M.D., 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. This work allowed the researchers to identify peanut allergy-specific loci “in the HLA-DR and -DQ gene region at 6p21.32, tagged by rs7192 and rs9275596, in 2,197 participants of European ancestry.”

The researchers replicated these associations in an independent sample of European ancestry. These associations, the researchers found, were further supported by metaanalyses across the discovery and replication samples. “This GWAS provides convincing evidence that the HLA-DR and -DQ gene region, as tagged by rs7192 or rs9275596, harbors significant genetic risk for PA in subjects of European ancestry,” noted the authors.

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.

“Both single-nucleotide polymorphisms (SNPs) are associated with differential DNA methylation levels at multiple CpG sites, and differential DNA methylation of the HLA-DQB1 and HLA-DRB1 genes partially mediate the identified SNP–[peanut allergy] associations,” the researchers indicated.

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,” Dr. Wang said. “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.”