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Original article
Contribution of the MHC region to the familial risk of coeliac disease
  1. S Bevana,
  2. S Popata,
  3. C P Braeggerb,
  4. A Buschc,
  5. D O’Donoghued,
  6. K Falth-Magnussone,
  7. A Fergusonf,
  8. A Godking,
  9. L Hogbergh,
  10. G Holmesi,
  11. K B Hosiej,
  12. P D Howdlek,
  13. H Jenkinsl,
  14. D Jewellg,
  15. S Johnstonm,
  16. N P Kennedyn,
  17. G Kerro,
  18. P Kumarp,
  19. R F A Loganq,
  20. A H G Lovem,
  21. M Marshr,
  22. C J J Mulders,
  23. K Sjobergt,
  24. L Stenhammerh,
  25. J Walker-Smithu,
  26. A M Marossya,
  27. R S Houlstona
  1. aSection of Cancer Genetics, Institute of Cancer Research, 15 Cotswold Road, Sutton, Surrey, SM2 5NG, UK, bUniversity Children’s Hospital, Steinwiesstrasse 75, Zurich, Switzerland, cUniversity Children’s Hospital, Eberhard-Karls-Universitat, Tubingen, Germany, dGastroenterology and Liver Unit, St Vincent’s Hospital, Dublin, Ireland, eDepartment of Paediatrics, Linkoping University, Sweden, fDepartment of Medicine, Western General Hospital, Edinburgh, UK, gGastroenterology Unit, The Radcliffe Infirmary, Oxford, UK, hDepartment of Gastroenterology, Norrkoping Hospital, Sweden, iDepartment of Medicine, Derbyshire Royal Infirmary, Derby, UK, jUniversity Surgical Unit, Northern General Hospital, Sheffield, UK, kDivision of Medicine, St James’s University Hospital, Leeds, UK, lDepartment of Child Health, University Hospital of Wales, Cardiff, UK, mDepartment of Medicine, The Queen’s University of Belfast, Belfast, UK, nDepartment of Clinical Medicine, St James’s Hospital, Dublin, Ireland, oGastroenterology Unit, Royal Shrewsbury Hospital, Shrewsbury, UK, pDepartment of Gastroenterology, St Bartholomew’s Hospital, London, UK, qDepartment of Public Health and Epidemiology, University Hospital, Nottingham, UK, rUniversity Department of Medicine, Hope Hospital, Salford, Manchester, UK, sHepatogastroenterology, Rijnstate Hospital, Arnhem, The Netherlands, tDepartment of Medicine, University of Lund, Malmo, Sweden, uUniversity Department of Paediatric Gastroenterology, Royal Free Hospital, London, UK
  1. Dr Houlston.

Abstract

Susceptibility to coeliac disease is genetically determined by possession of specific HLA-DQ alleles, acting in concert with one or more non-HLA linked genes. The pattern of risk seen in sibs and twins in coeliac disease is most parsimonious with a multiplicative model for the interaction between the two classes of genes. Based on a sib recurrence risk for coeliac disease of 10% and a population prevalence of 0.0033, the sib relative risk is 30. To evaluate the contribution of the MHC region to the familial risk of coeliac disease, we have examined haplotype sharing probabilities across this region in 55 coeliac disease families. Based on these probabilities the sib relative risk of coeliac disease associated with the MHC region is 3.7. Combining these results with published data on allele sharing at HLA, the estimated sib relative risk associated with the MHC region is 3.3. Therefore, the MHC genes contribute no more than 40% of the sib familial risk of coeliac disease and the non-HLA linked gene (or genes) are likely to be the stronger determinant of coeliac disease susceptibility.

  • coeliac disease
  • familial risk
  • MHC

https://doi.org/10.1136/jmg.36.9.687

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