A two-marker haplotype in the IRF5 gene is associated with inflammatory bowel disease in a North American cohort

Genes Immun. 2012 Jun;13(4):351-5. doi: 10.1038/gene.2011.90. Epub 2012 Jan 19.


Interferon regulatory factor 5 (IRF5) located on human chromosome 7q32 is associated with many chronic inflammatory disorders. IRF5 is the key regulator of proinflammatory cytokines and type I interferons. We surveyed two cohorts of inflammatory bowel disease (IBD) patients from a North American Consortium. Six single-nucleotide polymorphisms and a 5-base-pair (bp) insertion-deletion (CGGGG indel)polymorphism were investigated. Cytokine secretion was measured in primary lymphocytes after toll-like receptor 9 stimulation. Two-marker haplotypes containing the pairs (rs4728142-CGGGG indel) and (CGGGG indel-rs7808907) were associated with IBD protection (P=2.89 × 10(-6), P=9.32 × 10(-4) (non-Jewish ancestry) and P=4.68 × 10(-8), P=2.50 × 10(-8) (Jewish ancestry)) and IBD risk (P=0.004, P=0.003 (Jewish ancestry), respectively. IRF5 polymorphisms were risk factors for IBD in a single cohort. Interleukin-12-p70 cytokine production was higher (P=0.04) in lymphocytes from controls with two alleles of the 5-bp insertion. IRF5 polymorphisms contribute to the risk profile for Crohn's disease and ulcerative colitis along with ancestry and NOD2 genotypes.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Alleles
  • Case-Control Studies
  • Cohort Studies
  • Female
  • Genetic Markers
  • Genetic Predisposition to Disease*
  • Haplotypes*
  • Humans
  • INDEL Mutation
  • Inflammatory Bowel Diseases / epidemiology
  • Inflammatory Bowel Diseases / genetics*
  • Inflammatory Bowel Diseases / immunology
  • Interferon Regulatory Factors
  • Interleukin-12 / immunology
  • Logistic Models
  • Lymphocytes / immunology
  • Male
  • Middle Aged
  • North America / epidemiology
  • Polymorphism, Single Nucleotide
  • Risk Factors
  • Toll-Like Receptor 9 / immunology
  • Young Adult


  • Genetic Markers
  • IRF5 protein, human
  • Interferon Regulatory Factors
  • TLR9 protein, human
  • Toll-Like Receptor 9
  • Interleukin-12