Skip to main content
NCBI home page
American Journal of Human Genetics logoLink to American Journal of Human Genetics
. 1996 Jul;59(1):226–233.

Analysis of the contribution of HLA genes to genetic predisposition in inflammatory bowel disease.

I Naom 1, J Lee 1, D Ford 1, S J Bowman 1, J S Lanchbury 1, I Haris 1, S V Hodgson 1, D Easton 1, J Lennard-Jones 1, C G Mathew 1
PMCID: PMC1915114  PMID: 8659528

Abstract

Crohn disease (CD) and ulcerative colitis (UC) are chronic inflammatory bowel diseases (IBDs) of unknown etiology. First-degree relatives of IBD patients have a 10-fold increase in risk of developing the same disease, and distinct associations between specific HLA types and both CD and UC have been reported. We have evaluated the contribution of genes at the HLA locus to susceptibility in IBD by linkage analysis of highly informative microsatellite polymorphisms in 43 families with multiple affected cases. No evidence for linkage of HLA to IBD was obtained under any of the four models tested. Analysis of HLA haplotype sharing in affected relatives indicated that the relative risk to a sibling conferred by the HLA locus was 1.11 in UC and 0.75 in CD, with upper (95%) confidence limits of 2.41 and 1.37, respectively. This suggests that other genetic or environmental factors are responsible for most of the familial aggregation in IBD.

Full text

PDF
226

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Achord J. L., Gunn C. H., Jr, Jackson J. F. Regional enteritis and HLA concordance in multiple siblings. Dig Dis Sci. 1982 Apr;27(4):330–332. doi: 10.1007/BF01296752. [DOI] [PubMed] [Google Scholar]
  2. Asakura H., Tsuchiya M., Aiso S., Watanabe M., Kobayashi K., Hibi T., Ando K., Takata H., Sekiguchi S. Association of the human lymphocyte-DR2 antigen with Japanese ulcerative colitis. Gastroenterology. 1982 Mar;82(3):413–418. [PubMed] [Google Scholar]
  3. Colombel J. F., Guillemot F., Van Gossum A., Dufossé F., Cortot A., Dupont E., Paris J. C. Familial Crohn's disease in multiple siblings: no linkage to the HLA system. Gastroenterol Clin Biol. 1989 Aug-Sep;13(8-9):676–678. [PubMed] [Google Scholar]
  4. Hugot J. P., Laurent-Puig P., Gower-Rousseau C., Caillat-Zucman S., Beaugerie L., Dupas J. L., Van Gossum A., Bonäit-Pellie C., Cortot A., Thomas G. Linkage analyses of chromosome 6 loci, including HLA, in familial aggregations of Crohn disease. G.E.T.A.I.D. Am J Med Genet. 1994 Aug 15;52(2):207–213. doi: 10.1002/ajmg.1320520216. [DOI] [PubMed] [Google Scholar]
  5. Jongeneel C. V., Briant L., Udalova I. A., Sevin A., Nedospasov S. A., Cambon-Thomsen A. Extensive genetic polymorphism in the human tumor necrosis factor region and relation to extended HLA haplotypes. Proc Natl Acad Sci U S A. 1991 Nov 1;88(21):9717–9721. doi: 10.1073/pnas.88.21.9717. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Kobayashi K., Atoh M., Konoeda Y., Yagita A., Inoko H., Sekiguchi S. HLA-DR, DQ and T cell antigen receptor constant beta genes in Japanese patients with ulcerative colitis. Clin Exp Immunol. 1990 Jun;80(3):400–403. doi: 10.1111/j.1365-2249.1990.tb03300.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Kobayashi K., Atoh M., Yagita A., Konoeda Y., Inoko H., Ando A., Sekiguchi S. Crohn's disease in the Japanese is associated with the HLA-DRw53. Exp Clin Immunogenet. 1990;7(2):101–108. [PubMed] [Google Scholar]
  8. Küster W., Pascoe L., Purrmann J., Funk S., Majewski F. The genetics of Crohn disease: complex segregation analysis of a family study with 265 patients with Crohn disease and 5,387 relatives. Am J Med Genet. 1989 Jan;32(1):105–108. doi: 10.1002/ajmg.1320320122. [DOI] [PubMed] [Google Scholar]
  9. Lashner B. A., Evans A. A., Kirsner J. B., Hanauer S. B. Prevalence and incidence of inflammatory bowel disease in family members. Gastroenterology. 1986 Dec;91(6):1396–1400. doi: 10.1016/0016-5085(86)90193-9. [DOI] [PubMed] [Google Scholar]
  10. Lathrop G. M., Lalouel J. M., Julier C., Ott J. Strategies for multilocus linkage analysis in humans. Proc Natl Acad Sci U S A. 1984 Jun;81(11):3443–3446. doi: 10.1073/pnas.81.11.3443. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Meucci G., Vecchi M., Torgano G., Arrigoni M., Prada A., Rocca F., Curzio M., Pera A., de Franchis R. Familial aggregation of inflammatory bowel disease in northern Italy: a multicenter study. The Gruppo di Studio per le Malattie Infiammatorie Intestinali (IBD Study Group). Gastroenterology. 1992 Aug;103(2):514–519. doi: 10.1016/0016-5085(92)90841-l. [DOI] [PubMed] [Google Scholar]
  12. Monsén U., Bernell O., Johansson C., Hellers G. Prevalence of inflammatory bowel disease among relatives of patients with Crohn's disease. Scand J Gastroenterol. 1991 Mar;26(3):302–306. doi: 10.3109/00365529109025046. [DOI] [PubMed] [Google Scholar]
  13. Monsén U., Iselius L., Johansson C., Hellers G. Evidence for a major additive gene in ulcerative colitis. Clin Genet. 1989 Dec;36(6):411–414. [PubMed] [Google Scholar]
  14. Müllenbach R., Lagoda P. J., Welter C. An efficient salt-chloroform extraction of DNA from blood and tissues. Trends Genet. 1989 Dec;5(12):391–391. [PubMed] [Google Scholar]
  15. Olerup O., Zetterquist H. HLA-DR typing by PCR amplification with sequence-specific primers (PCR-SSP) in 2 hours: an alternative to serological DR typing in clinical practice including donor-recipient matching in cadaveric transplantation. Tissue Antigens. 1992 May;39(5):225–235. doi: 10.1111/j.1399-0039.1992.tb01940.x. [DOI] [PubMed] [Google Scholar]
  16. Orholm M., Iselius L., Sørensen T. I., Munkholm P., Langholz E., Binder V. Investigation of inheritance of chronic inflammatory bowel diseases by complex segregation analysis. BMJ. 1993 Jan 2;306(6869):20–24. doi: 10.1136/bmj.306.6869.20. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Orholm M., Munkholm P., Langholz E., Nielsen O. H., Sørensen T. I., Binder V. Familial occurrence of inflammatory bowel disease. N Engl J Med. 1991 Jan 10;324(2):84–88. doi: 10.1056/NEJM199101103240203. [DOI] [PubMed] [Google Scholar]
  18. Risch N. Linkage strategies for genetically complex traits. II. The power of affected relative pairs. Am J Hum Genet. 1990 Feb;46(2):229–241. [PMC free article] [PubMed] [Google Scholar]
  19. Satsangi J., Jewell D. P., Rosenberg W. M., Bell J. I. Genetics of inflammatory bowel disease. Gut. 1994 May;35(5):696–700. doi: 10.1136/gut.35.5.696. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Spielman R. S., McGinnis R. E., Ewens W. J. Transmission test for linkage disequilibrium: the insulin gene region and insulin-dependent diabetes mellitus (IDDM). Am J Hum Genet. 1993 Mar;52(3):506–516. [PMC free article] [PubMed] [Google Scholar]
  21. Strober W., Ehrhardt R. O. Chronic intestinal inflammation: an unexpected outcome in cytokine or T cell receptor mutant mice. Cell. 1993 Oct 22;75(2):203–205. doi: 10.1016/0092-8674(93)80062-j. [DOI] [PubMed] [Google Scholar]
  22. Toyoda H., Wang S. J., Yang H. Y., Redford A., Magalong D., Tyan D., McElree C. K., Pressman S. R., Shanahan F., Targan S. R. Distinct associations of HLA class II genes with inflammatory bowel disease. Gastroenterology. 1993 Mar;104(3):741–748. doi: 10.1016/0016-5085(93)91009-7. [DOI] [PubMed] [Google Scholar]
  23. Tysk C., Lindberg E., Järnerot G., Flodérus-Myrhed B. Ulcerative colitis and Crohn's disease in an unselected population of monozygotic and dizygotic twins. A study of heritability and the influence of smoking. Gut. 1988 Jul;29(7):990–996. doi: 10.1136/gut.29.7.990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Vaughan R. W., Lanchbury J. S., Marsh S. G., Hall M. A., Bodmer J. G., Welsh K. I. The application of oligonucleotide probes to HLA class II typing of the DRB sub-region. Tissue Antigens. 1990 Oct;36(4):149–155. doi: 10.1111/j.1399-0039.1990.tb01821.x. [DOI] [PubMed] [Google Scholar]
  25. Weber J. L., Kwitek A. E., May P. E., Zoghbi H. Y. Dinucleotide repeat polymorphism at the D6S105 locus. Nucleic Acids Res. 1991 Feb 25;19(4):968–968. doi: 10.1093/nar/19.4.968. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Weissenbach J., Gyapay G., Dib C., Vignal A., Morissette J., Millasseau P., Vaysseix G., Lathrop M. A second-generation linkage map of the human genome. Nature. 1992 Oct 29;359(6398):794–801. doi: 10.1038/359794a0. [DOI] [PubMed] [Google Scholar]
  27. Ziegle J. S., Su Y., Corcoran K. P., Nie L., Mayrand P. E., Hoff L. B., McBride L. J., Kronick M. N., Diehl S. R. Application of automated DNA sizing technology for genotyping microsatellite loci. Genomics. 1992 Dec;14(4):1026–1031. doi: 10.1016/s0888-7543(05)80126-0. [DOI] [PubMed] [Google Scholar]

Articles from American Journal of Human Genetics are provided here courtesy of American Society of Human Genetics

RESOURCES