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Identification of novel polymorphisms in the β7 integrin gene: family-based association studies in inflammatory bowel disease

Genes & Immunity volume 2, pages 455–460 (2001)Cite this article

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 β7 integrin ameliorate colitis in animal models. We obtained genomic sequence for β7 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 ⩾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.

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Acknowledgements

David van Heel is a Medical Research Council Clinical Training Fellow. We thank all participating families, our research nurses Heather Holt, Daphne Lever and Sue Goldthorpe, the National Association for Crohn’s and Colitis, and consultants and general practitioners who helped ascertain families.

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Authors and Affiliations

  1. Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford, OX3 7BN, UK

    DA van Heel

  2. Gastroenterology Unit, Gibson Laboratories, Radcliffe Infirmary, Oxford, OX2 6HE, UK

    DA van Heel & DP Jewell

  3. Oxagen Ltd, 91 Milton Park, Abingdon, OX14 4RY, UK

    AH Carey

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  1. DA van Heel
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  2. AH Carey
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  3. DP Jewell
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Correspondence to DA van Heel.

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Part of this work was funded by Oxagen Ltd, and a Medical Research Council LINK grant between the University of Oxford and Oxagen Ltd.

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van Heel, D., Carey, A. & Jewell, D. Identification of novel polymorphisms in the β7 integrin gene: family-based association studies in inflammatory bowel disease . Genes Immun 2, 455–460 (2001). https://doi.org/10.1038/sj.gene.6363810

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