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FUT2 Variants Confer Susceptibility to Familial Otitis Media.

Regie Lyn P Santos-Cortez1, Charlotte M Chiong2, Daniel N Frank3

  • 1Department of Otolaryngology, University of Colorado School of Medicine (CUSOM), Aurora, CO 80045, USA; Center for Children's Surgery, Children's Hospital Colorado (CHCO), Aurora, CO 80045, USA; Philippine National Ear Institute, University of the Philippines (UP) Manila - National Institutes of Health (NIH), Manila 1000, Philippines.

American Journal of Human Genetics
|November 8, 2018
PubMed
Summary

Genetic variants in the FUT2 gene influence susceptibility to otitis media (middle ear infections). These FUT2 variants alter A antigen levels, impacting the middle ear microbiome and disease risk.

Keywords:
16S rRNA sequencingA antigenFUT2TDTfucosyltransferasemicrobiomemiddle ear infectionotitis mediatransient expressiontransmission disequilibrium test

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Area of Science:

  • Genetics
  • Microbiology
  • Otolaryngology

Background:

  • Non-secretor status, linked to FUT2 gene variants, affects autoimmune disease risk and protection against viral infections.
  • The role of the FUT2 gene in otitis media (middle ear infection) susceptibility requires further investigation.

Purpose of the Study:

  • To determine the association between FUT2 gene variants and otitis media susceptibility.
  • To investigate the functional impact of FUT2 variants on middle ear physiology and microbiome.

Main Methods:

  • DNA analysis of 609 multi-ethnic families and case subjects with otitis media.
  • Exome and Sanger sequencing, linkage analysis, and transmission disequilibrium tests (TDT).
  • Assessment of A antigen expression and middle ear microbiota composition in relation to FUT2 variants.

Main Results:

  • A common FUT2 variant (c.604C>T) co-segregated with otitis media in a Filipino family.
  • A rare FUT2 variant (c.412C>T) and the common c.461G>A variant were associated with otitis media in US trios.
  • FUT2 variants altered A antigen levels and significantly modified middle ear microbiota composition and biodiversity.
  • Combined analysis of FUT2 missense and nonsense variants showed significant over-transmission in trios.

Conclusions:

  • Both common and rare FUT2 variants contribute to otitis media susceptibility.
  • FUT2 variants likely influence otitis media risk by altering A antigen expression and subsequently modifying the middle ear microbiome.
  • Otitis media is a complex trait influenced by genetic heterogeneity and environmental factors.