Copy number variation of the beta defensin gene cluster on chromosome 8p influences the bacterial microbiota within the nasopharynx of otitis-prone children

Eric A. Jones, Anchasa Kananurak, Charles L Bevins, Edward J. Hollox, Lauren O. Bakaletz

Research output: Contribution to journalArticle

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Abstract

As there is increasing evidence that aberrant defensin expression is related to susceptibility for infectious disease and inflammatory disorders, we sought to determine if copy number of the beta-defensin gene cluster located on chromosome 8p23.1 (DEFB107, 106, 105, 104, 103, DEFB4 and SPAG11), that shows copy number variation as a block, was associated with susceptibility to otitis media (OM). The gene DEFB103 within this complex encodes human beta defensin-3 (hBD-3), an antimicrobial peptide (AP) expressed by epithelial cells that line the mammalian airway, important for defense of mucosal surfaces and previously shown to have bactericidal activity in vitro against multiple human pathogens, including the three that predominate in OM. To this end, we conducted a retrospective case-control study of 113 OM prone children and 267 controls aged five to sixty months. We identified the copy number of the above defined beta-defensin gene cluster (DEFBCN) in each study subject by paralogue ratio assays. The mean DEFB-CN was indistinguishable between subjects classified as OM prone based on a recent history of multiple episodes of OM and control subjects who had no history of OM (4.4±0.96 versus 4.4±1.08, respectively: Odds Ratio [OR]: 1.16 (95% CI: 0.61, 2.20). Despite a lack of direct association, we observed a statistically significant correlation between DEFB-CN and nasopharyngeal bacterial colonization patterns. Collectively, our findings suggested that susceptibility to OM might be mediated by genetic variation among individuals, wherein a DEFB-CN less than 4 exerts a marked influence on the microbiota of the nasopharynx, specifically with regard to colonization by the three predominant bacterial pathogens of OM.

Original languageEnglish (US)
Article numbere98269
JournalPLoS One
Volume9
Issue number5
DOIs
StatePublished - May 27 2014

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beta-Defensins
nasopharynx
Otitis
otitis media
Nasopharynx
Microbiota
Otitis Media
Chromosomes
Multigene Family
multigene family
Genes
Pathogens
chromosomes
Defensins
Assays
Association reactions
Peptides
bacterial colonization
microbiome
otitis

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Copy number variation of the beta defensin gene cluster on chromosome 8p influences the bacterial microbiota within the nasopharynx of otitis-prone children. / Jones, Eric A.; Kananurak, Anchasa; Bevins, Charles L; Hollox, Edward J.; Bakaletz, Lauren O.

In: PLoS One, Vol. 9, No. 5, e98269, 27.05.2014.

Research output: Contribution to journalArticle

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