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Inflammatory bowel disease
Fine mapping of the chromosome 3p susceptibility locus in inflammatory bowel disease
  1. J Hampea,
  2. N J Lyncha,
  3. S Danielsb,
  4. S Bridgerc,
  5. A J S Macphersonc,
  6. P Stokkersd,
  7. A Forbesf,
  8. J E Lennard-Jonesf,
  9. C G Mathewe,
  10. M E Curranb,
  11. S Schreibera
  1. aIst Medical Department, Christian-Albrechts- University, Kiel, Germany, bAxys Pharmaceuticals Inc., La Jolla, California, USA, cKing's College School of Medicine, London, UK, dAcademic Medical Centre, Amsterdam, the Netherlands, eDivision of Medical and Molecular Genetics, GKT Medical School, Guy's Hospital, London, UK, fSt Mark's Hospital, Harrow, UK
  1. Professor S Schreiber, Ist Department of Medicine, Christian-Albrechts- Universtität Kiel, Schittenhelmstr. 12, D-24105 Kiel, Germany.s.schreiber{at}mucosa.de

Abstract

BACKGROUND AND AIMS Genetic predisposition for inflammatory bowel disease (IBD) has been demonstrated by epidemiological and genetic linkage studies. Genetic linkage of IBD to chromosome 3 has been observed previously. A high density analysis of chromosome 3p was performed to confirm prior linkages and elucidate potential genetic associations.

METHODS Forty three microsatellite markers on chromosome 3 were genotyped in 353 affected sibling pairs of North European Caucasian extraction (average marker density 2 cM in the linkage interval). Marker order was defined by genetic and radiation hybrid techniques.

RESULTS The maximum single point logarithm of odds (LOD) score was observed for Crohn's disease at D3S3591. Peak multipoint LOD scores of 1.65 and 1.40 for the IBD phenotype were observed near D3S1304 (distal 3p) and near D3S1283 in the linkage region previously reported. Crohn's disease contributed predominantly to the linkage. The transmission disequilibrium test showed significant evidence of association (p=0.009) between allele 4 of D3S1076 and the IBD phenotype (51 transmittedv 28 non-transmitted). Two known polymorphisms in the CCR2 and CCR5 genes were analysed, neither of which showed significant association with IBD. Additional haplotype associations were observed in the vicinity of D3S1076.

CONCLUSIONS This study provides confirmatory linkage evidence for an IBD susceptibility locus on chromosome 3p and suggests that CCR2 and CCR5 are unlikely to be major susceptibility loci for IBD. The association findings in this region warrant further investigation.

  • inflammatory bowel disease
  • fine mapping
  • chromosome 3

  • Abbreviations used in this paper

    IBD
    inflammatory bowel disease
    CD
    Crohn's disease
    UC
    ulcerative colitis
    HIV
    human immunodeficiency virus
    PCR
    polymerase chain reaction
    LOD
    logarithm of odds
    TDT
    transmission disequilibrium test
    IL5RA
    interleukin 5 receptor alpha

    • https://doi.org/10.1136/gut.48.2.191

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    • Abbreviations used in this paper

      IBD
      inflammatory bowel disease
      CD
      Crohn's disease
      UC
      ulcerative colitis
      HIV
      human immunodeficiency virus
      PCR
      polymerase chain reaction
      LOD
      logarithm of odds
      TDT
      transmission disequilibrium test
      IL5RA
      interleukin 5 receptor alpha
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