Genetic Variants May Be Tied to Otitis Media Risk

By David Douglas

November 12, 2018

NEW YORK (Reuters Health) - Population-specific FUT2 variants appear to confer risk for otitis media susceptibility in multiple cohorts of different ethnicity, according to a multinational group of researchers.

"We predict that FUT2 is one of numerous genes with variants that make one prone to middle ear infections, and our goal is to eventually identify as many genes and variants as possible in various populations so we can predict who is at risk for infection and requires more careful management," Dr. Regie Santos-Cortez of the University of Colorado School of Medicine, in Aurora, told Reuters Health by email.

For the study, online October 25 in The American Journal of Human Genetics, Dr. Santos-Cortez and colleagues obtained DNA samples from 609 multi-ethnic families and simplex cases with otitis media. Those with known genetic, craniofacial and immunodeficiency syndromes were excluded.

The researchers found that a population-specific FUT2 variant c.604C>T (p.Arg202*) is a risk factor for otitis media susceptibility in indigenous Filipinos who are A2ML1-negative.

They also identified additional missense variants in European-American and Pakistani families with recurrent acute or chronic otitis media. In addition, they determined that the c.461G>A (p.Trp154*) variant likewise confers otitis media risk and induces shifts in the middle ear microbiome.

The transient expression of FUT2 in the middle ear mucosa during acute otitis media, they note, "implies that the mechanism by which FUT2 variants affect middle ear function mainly occurs during active infection."

"If you have these mutations," Dr. Santos-Cortez said in a statement, "you will have a slightly different microbiota which could elevate the risk of disease."

Further information on FUT2 expression in the middle ear was derived from microarray analysis of mRNA from healthy control mice compared to mice that had acute otitis media after inoculation with H. influenzae. FUT2 expression was increased in infected mouse middle ear.

FUT2 controls surface expression of A and B antigens and their precursor H antigen in mucosal epithelia, and the team also found lower FUT2 and A antigen levels in cells transfected with FUT2 variants.

Thus, they say, "Common and rare FUT2 variants confer susceptibility to otitis media, likely by modifying the middle ear microbiome through regulation of A antigen levels in epithelial cells."

Summing up, Dr. Santos-Cortez concluded, "Changing the middle ear microbiome is just one way by which genetic variants affect the middle ear but is interesting because in the future it is a potential avenue for improving middle ear health."


Am J Hum Genet 2018.