CHOP researchers pinpoint genetic variant associated with bacterial ear infection in children

A middle ear infection is a common illness and is associated with acute pain, especially in children growing up. Researchers at the Children’s Hospital of Philadelphia (CHOP) have recently discovered a DNA variant that is associated with the illness; it may offer an earlier clue to doctors and allow them to treat it early.

In a collaboration with the University Medical Center Rotterdam in the Netherlands, Hakon Hakonarson headed up the research at CHOP and published his team’s findings in the journal Nature Communications.

Acute otitis media (AOM) is the clinical term for a middle ear infection, and because of the bacterial inflammation children frequently require a round of antibiotic treatment. The risk of developing AOM depends on environmental inputs as well as clear genetic risk factors.

"Although microbes cause this condition, it's been well known that genetics also plays a role," said Hakonarson in a statement. "This is the first and largest genetic study focused on risk susceptibility for acute otitis media."

The researchers studied 11,000 children under the age of 3, consisting of both AOM patients and control groups. They undertook a genome-wide association study (GWAS) to scan the infants' DNA for variants associated with the disease, picking out a single-nucleotide polymorphism (SNP), which is a single-base letter change, at a position on chromosome 6.

In mouse experiments, they then linked the SNP with the methylation of a gene called FNDC1, important because methylation can regulate how genes are expressed. They indeed found an inverse correlation between methylation of FNDC1 and the expression of the gene itself, serving as a mechanistic insight into how a single SNP may alter the course of disease.

They also explain that although FNDC1 hasn’t been well-studied, it has been linked to inflammation, and this study implicates FNDC1 in the pathogenesis of AOM through an altered immune or inflammatory response.

"Although the gene's function in humans has not been well studied, we do know that FNDC1 codes for a protein with a role in inflammation," said Hakonarson.

This study is important because it may lead to targeting AOM with more specific therapies, as well as giving doctors a better insight into treating those with this genetic susceptibility earlier, before the child experiences pain.