MAST3: A novel IBD risk factor that modulates TLR4 signaling

C. Labbé, P. Goyette, C. Lefebvre, C. Stevens, T. Green, M. K. Tello-Ruiz, Z. Cao, A. L. Landry, J. Stempak, V. Annese, A. Latiano, S. R. Brant, R. H. Duerr, K. D. Taylor, J. H. Cho, A. H. Steinhart, M. J. Daly, M. S. Silverberg, R. J. Xavier, J. D. Rioux

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

Inflammatory bowel disease (IBD) is a chronic disorder caused by multiple factors in a genetically susceptible host. Significant advances in the study of genetic susceptibility have highlighted the importance of the innate immune system in this disease. We previously completed a genome-wide linkage study and found a significant locus (IBD6) on chromosome 19 p. We were interested in identifying the causal variant in IBD6. We performed a two-stage association mapping study. In stage 1, 1530 single-nucleotide polymorphisms (SNPs) were selected from the HapMap database and genotyped in 761 patients with IBD. Among the SNPs that passed the threshold for replication, 26 were successfully genotyped in 754 additional patients (stage 2). One intronic variant, rs273506, located in the microtubule-associated serine/threonine-protein kinase gene-3 (MAST3), was found to be associated in both stages (pooled P = 1.8 × 10-4). We identified four MAST3 coding variants, including a non-synonymous SNP rs8108738, correlated to rs273506 and associated with IBD. To test whether MAST3 was expressed in cells of interest, we performed expression assays, which showed abundant expression of MAST3 in antigen-presenting cells and in lymphocytes. The knockdown of MAST3 specifically decreased Toll-like receptor-4-dependent NF-κB activity. Our findings are additional proofs of the pivotal role played by modulators of NF-κB activity in IBD pathogenesis.

Original languageEnglish (US)
Pages (from-to)602-612
Number of pages11
JournalGenes and immunity
Volume9
Issue number7
DOIs
StatePublished - 2008
Externally publishedYes

ASJC Scopus subject areas

  • Immunology
  • Genetics
  • Genetics(clinical)

Fingerprint

Dive into the research topics of 'MAST3: A novel IBD risk factor that modulates TLR4 signaling'. Together they form a unique fingerprint.

Cite this