title: Identification of novel polymorphisms in the beta7 integrin gene: family-based association studies in inflammatory bowel disease.
abstract: Linkage studies from five groups worldwide have confirmed the presence of an inflammatory bowel disease susceptibility locus on chromosome 12q. Beta 7 integrin is a strong candidate gene within this region, and is involved in lymphocyte homing to the gut and retention of intra-epithelial lymphocytes. Monoclonal antibodies to beta7 integrin ameliorate colitis in animal models. We obtained genomic sequence for beta7 integrin, and screened all 16 exons and 1.7 kb of 5' promoter region for polymorphisms in 24 individuals. Fourteen single nucleotide polymorphisms were identified in total and, of these, two common (frequency > or =10%) intronic and two amino acid changing polymorphisms were assessed for potential disease associations. Data were available from 102 multiply affected inflammatory bowel disease families (affected sibling pairs) and 362 simplex (one affected proband) families containing 254 ulcerative colitis, 13 indeterminate colitis and 300 Crohn's disease trios (parents + affected child). No significant associations with any disease phenotype were found with the transmission disequilibrium test. Beta 7 integrin is unlikely to be involved in the genetic susceptibility to inflammatory bowel disease, and therefore future studies on chromosome 12 should focus on other positional candidate genes.
authors.affiliation: Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford, OX3 7BN, UK. david.vanheel@well.ox.ac.uk
authors.forename: D A
authors.initials: DA
authors.lastname: van Heel
authors.forename: A H
authors.initials: AH
authors.lastname: Carey
authors.forename: D P
authors.initials: DP
authors.lastname: Jewell
mesh_terms: D002874:Chromosome Mapping; D002881:Chromosomes, Human, Pair 12; D005260:Female; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D005828:Genetics, Population; D005838:Genotype; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000235:genetics*; D039641:Integrin beta Chains; D016023:Integrins / Q000235:genetics*; D008297:Male; D009154:Mutation; D020641:Polymorphism, Single Nucleotide
chemical_list: D005819:Genetic Markers; D039641:Integrin beta Chains; D016023:Integrins; C091368:integrin beta7