Targeted resequencing identifies defective variants of decoy receptor 3 in pediatric-onset inflammatory bowel disease

C. J. Cardinale, Z. Wei, S. Panossian, F. Wang, C. E. Kim, F. D. Mentch, R. M. Chiavacci, K. E. Kachelries, R. Pandey, S. F.A. Grant, R. N. Baldassano, H. Hakonarson

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

Genome-wide association studies have implicated common variation at the 20q13 locus in inflammatory bowel disease, particularly for the pediatric Crohn's form. This locus harbors tumor necrosis factor receptor superfamily (TNFRSF6B), encoding a secreted protein, decoy receptor 3 (DcR3), which binds to and neutralizes pro-inflammatory cytokines of the tumor necrosis factor superfamily. We sought to further the evidence of DcR3's role in pediatric IBD by identifying missense mutations with functional significance within TNFRSF6B. We sequenced the exons of the gene in 528 Caucasian pediatric IBD cases and 549 Caucasian healthy controls to establish the frequency of such events in each population. Sequencing revealed that our IBD cohort harbored a greater number of missense variants, yielding an odds ratio of 3.9 (P-value=0.005). Using functional assays, we established that the frequency of mutants defective in secretion from cultured cells was greater in the Crohn's category than in the controls, yielding an odds ratio of 7.1 (P-value=0.004). These results suggest that rare defective variants in TNFRSF6B have a role in the pathogenesis of some cases of IBD and that interventions targeting this group of tumor necrosis factor-family members may benefit patients with IBD.

Original languageEnglish (US)
Pages (from-to)447-452
Number of pages6
JournalGenes and Immunity
Volume14
Issue number7
DOIs
StatePublished - Aug 23 2013

All Science Journal Classification (ASJC) codes

  • Immunology
  • Genetics
  • Genetics(clinical)

Keywords

  • DcR3
  • GWAS
  • TNFRSF6B
  • inflammatory bowel disease
  • sequencing

Fingerprint Dive into the research topics of 'Targeted resequencing identifies defective variants of decoy receptor 3 in pediatric-onset inflammatory bowel disease'. Together they form a unique fingerprint.

Cite this