FBXO11, a regulator of the TGFΒ pathway, is associated with severe otitis media in Western Australian children

M. S. Rye, S. P. Wiertsema, E. S H Scaman, John Oommen, W. Sun, R. W. Francis, W C Ang, C. E. Pennell, D. Burgner, Peter Richmond, Sarojini Vijayasekaran, H. L. Coates, S. D. Brown, Jenefer M Blackwell, S. E. Jamieson

Research output: Contribution to journalArticleResearchpeer-review

38 Citations (Scopus)


Otitis media (OM) is a common childhood disease characterised by middle ear inflammation following infection. Susceptibility to recurrent acute OM (rAOM) and chronic OM with effusion (COME) is highly heritable. Two murine mutants, Junbo and Jeff, spontaneously develop severe OM with similar phenotypes to human disease. Fine-mapping of these mutants identified two genes (Evi1 and Fbxo11) that interact with the transforming growth factor Β (TGFΒ) signalling pathway. We investigated these genes, as well as four Sma-and Mad-related (SMAD) genes of the TGFΒ pathway, as candidate rAOM/COME susceptibility genes in two predominantly Caucasian populations. Single-nucleotide polymorphisms (SNPs) within FBXO11 (family-based association testing Z-Score=2.61; P best=0.009) were associated with severe OM in family-based analysis of 434 families (561 affected individuals) from the Western Australian Family Study of OM. The FBXO11 association was replicated by directed analysis of Illumina 660W-Quad Beadchip data available for 253 cases and 866 controls (OR=1.55 (95% CI 1.28-1.89); P best = 6.9 × 10 -6) available within the Western Australian Pregnancy Cohort (Raine) Study. Combined primary and replication results show P combined= 2.98 × 10 -6. Neither cohort showed an association with EVI1 variants. Family-based associations at SMAD2 (P=0.038) and SMAD4 (P=0.048) were not replicated. Together, these data provide strong evidence for FBXO11 as a susceptibility gene for severe OM.

Original languageEnglish
Pages (from-to)352-359
Number of pages8
JournalGenes and Immunity
Issue number5
Publication statusPublished - Jul 2011
Externally publishedYes


  • Acute otitis media
  • association
  • genetic polymorphisms
  • mouse-to-man
  • otitis media with effusion
  • Raine Study

Cite this