title: Inflammatory bowel disease: the role of inflammatory cytokine gene polymorphisms.
abstract: The mechanisms responsible for development of inflammatory bowel disease (IBD) have not been fully elucidated, although the main cause of disease pathology is attributed to up-regulated inflammatory processes. The aim of this study was to investigate frequencies of polymorphisms in genes encoding pro-inflammatory and anti-inflammatory markers in IBD patients and controls. We determined genotypes of patients with IBD (n= 172) and healthy controls (n= 389) for polymorphisms in genes encoding various cytokines (interleukin (IL)-1beta, IL-6, tumour necrosis factor (TNF), IL-10, IL-1 receptor antagonist). Association of these genotypes to disease incidence and pathophysiology was investigated. No strong association was found with occurrence of IBD. Variation was observed between the ulcerative colitis study group and the control population for the TNF-alpha-308 polymorphism (p= 0.0135). There was also variation in the frequency of IL-6-174 and TNF-alpha-308 genotypes in the ulcerative colitis group compared with the Crohn's disease group (p= 0.01). We concluded that polymorphisms in inflammatory genes are associated with variations in IBD phenotype and disease susceptibility. Whether the polymorphisms are directly involved in regulating cytokine production, and consequently pathophysiology of IBD, or serve merely as markers in linkage disequilibrium with susceptibility genes remains unclear.
authors.affiliation: Thrombosis and Haemostasis Laboratory, Institute of Molecular Medicine, St James's Hospital, Dublin 8, Ireland.
authors.forename: Joanna
authors.initials: J
authors.lastname: Balding
authors.forename: Wendy J
authors.initials: WJ
authors.lastname: Livingstone
authors.forename: Judith
authors.initials: J
authors.lastname: Conroy
authors.forename: Lesley
authors.initials: L
authors.lastname: Mynett-Johnson
authors.forename: Donald G
authors.initials: DG
authors.lastname: Weir
authors.forename: Nasir
authors.initials: N
authors.lastname: Mahmud
authors.forename: Owen P
authors.initials: OP
authors.lastname: Smith
mesh_terms: D000328:Adult; D017668:Age of Onset; D001483:Base Sequence; D016207:Cytokines / Q000235:genetics; D017931:DNA Primers; D005260:Female; D005838:Genotype; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000276:immunology; D015212:Inflammatory Bowel Diseases / Q000235:genetics* / Q000276:immunology*; D007375:Interleukin-1 / Q000235:genetics; D016753:Interleukin-10 / Q000235:genetics; D017370:Interleukin-11 / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics; D008297:Male; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: D016207:Cytokines; D017931:DNA Primers; D007375:Interleukin-1; D017370:Interleukin-11; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10