title: A two-marker haplotype in the IRF5 gene is associated with inflammatory bowel disease in a North American cohort.
abstract: 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.
authors.affiliation: Department of Pediatrics, Stony Brook Medical Center, Stony Brook, NY 11794, USA. grace.gathungu@stonybrook.edu
authors.forename: G
authors.initials: G
authors.lastname: Gathungu
authors.forename: C K
authors.initials: CK
authors.lastname: Zhang
authors.forename: W
authors.initials: W
authors.lastname: Zhang
authors.forename: J H
authors.initials: JH
authors.lastname: Cho
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D054643:INDEL Mutation; D015212:Inflammatory Bowel Diseases / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology; D050835:Interferon Regulatory Factors; D018664:Interleukin-12 / Q000276:immunology; D016015:Logistic Models; D008214:Lymphocytes / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009656:North America / Q000453:epidemiology; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D051217:Toll-Like Receptor 9 / Q000276:immunology; D055815:Young Adult
chemical_list: D005819:Genetic Markers; C431713:IRF5 protein, human; D050835:Interferon Regulatory Factors; C495371:TLR9 protein, human; D051217:Toll-Like Receptor 9; D018664:Interleukin-12