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. 1991 Jan;83(1):74–78. doi: 10.1111/j.1365-2249.1991.tb05591.x

Molecular analysis of HLA-DQ A alleles in coeliac disease lack of a unique disease-associated sequence.

V Mantovani 1, G R Corazza 1, G Angelini 1, L Delfino 1, M Frisoni 1, P Mirri 1, R A Valentini 1, P Barboni 1, G Gasbarrini 1, G B Ferrara 1
PMCID: PMC1535481  PMID: 1671007

Abstract

Susceptibility to coeliac disease is strongly associated with some HLA class II antigens, encoded by the HLA-D region. Since the HLA-DQ locus seems to be primarily involved, we have analysed by polymerase chain reaction amplification and allele-specific oligonucleotide hybridization the most polymorphic region of the HLA-DQ A1 gene. No difference was observed between the 20 coeliac patients and 20 HLA-D-matched healthy controls who took part in the study. Furthermore, in patients and controls, the restriction fragment length polymorphism analysis of the HLA-DQ A gene using the restriction enzyme BglII did not disclose any specific disease-associated fragment. Our results are not consistent with a unique DQ A coeliac disease-associated sequence, but rather with the hypothesis that some polymorphic residues or allelic hypervariable regions, although found also in the normal population, can predispose to coeliac disease due to their higher frequency in this condition.

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Selected References

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

  1. Auffray C., Lillie J. W., Korman A. J., Boss J. M., Fréchin N., Guillemot F., Cooper J., Mulligan R. C., Strominger J. L. Structure and expression of HLA-DQ alpha and -DX alpha genes: interallelic alternate splicing of the HLA-DQ alpha gene and functional splicing of the HLA-DQ alpha gene using a retroviral vector. Immunogenetics. 1987;26(1-2):63–73. doi: 10.1007/BF00345456. [DOI] [PubMed] [Google Scholar]
  2. Bodmer J. G., Marsh S. G., Albert E. Nomenclature for factors of the HLA system, 1989. Immunol Today. 1990 Jan;11(1):3–10. doi: 10.1016/0167-5699(90)90003-r. [DOI] [PubMed] [Google Scholar]
  3. Brown J. H., Jardetzky T., Saper M. A., Samraoui B., Bjorkman P. J., Wiley D. C. A hypothetical model of the foreign antigen binding site of class II histocompatibility molecules. Nature. 1988 Apr 28;332(6167):845–850. doi: 10.1038/332845a0. [DOI] [PubMed] [Google Scholar]
  4. Bugawan T. L., Angelini G., Larrick J., Auricchio S., Ferrara G. B., Erlich H. A. A combination of a particular HLA-DP beta allele and an HLA-DQ heterodimer confers susceptibility to coeliac disease. Nature. 1989 Jun 8;339(6224):470–473. doi: 10.1038/339470a0. [DOI] [PubMed] [Google Scholar]
  5. Corazza G. R., Tabacchi P., Frisoni M., Prati C., Gasbarrini G. DR and non-DR Ia allotypes are associated with susceptibility to coeliac disease. Gut. 1985 Nov;26(11):1210–1213. doi: 10.1136/gut.26.11.1210. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Feinberg A. P., Vogelstein B. "A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity". Addendum. Anal Biochem. 1984 Feb;137(1):266–267. doi: 10.1016/0003-2697(84)90381-6. [DOI] [PubMed] [Google Scholar]
  7. Horn G. T., Bugawan T. L., Long C. M., Erlich H. A. Allelic sequence variation of the HLA-DQ loci: relationship to serology and to insulin-dependent diabetes susceptibility. Proc Natl Acad Sci U S A. 1988 Aug;85(16):6012–6016. doi: 10.1073/pnas.85.16.6012. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Howell M. D., Smith J. R., Austin R. K., Kelleher D., Nepom G. T., Volk B., Kagnoff M. F. An extended HLA-D region haplotype associated with celiac disease. Proc Natl Acad Sci U S A. 1988 Jan;85(1):222–226. doi: 10.1073/pnas.85.1.222. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Kagnoff M. F., Austin R. K., Hubert J. J., Bernardin J. E., Kasarda D. D. Possible role for a human adenovirus in the pathogenesis of celiac disease. J Exp Med. 1984 Nov 1;160(5):1544–1557. doi: 10.1084/jem.160.5.1544. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Kagnoff M. F., Harwood J. I., Bugawan T. L., Erlich H. A. Structural analysis of the HLA-DR, -DQ, and -DP alleles on the celiac disease-associated HLA-DR3 (DRw17) haplotype. Proc Natl Acad Sci U S A. 1989 Aug;86(16):6274–6278. doi: 10.1073/pnas.86.16.6274. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Mearin M. L., Biemond I., Peña A. S., Polanco I., Vazquez C., Schreuder G. T., de Vries R. R., van Rood J. J. HLA-DR phenotypes in Spanish coeliac children: their contribution to the understanding of the genetics of the disease. Gut. 1983 Jun;24(6):532–537. doi: 10.1136/gut.24.6.532. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Morellini M., Trabace S., Mazzilli M. C., Lulli P., Cappellacci S., Bonamico M., Margarit I., Gandini E. A study of HLA class II antigens in an Italian paediatric population with coeliac disease. Dis Markers. 1988 Mar;6(1):23–28. [PubMed] [Google Scholar]
  13. Roep B. O., Bontrop R. E., Peña A. S., van Eggermond M. C., van Rood J. J., Giphart M. J. An HLA-DQ alpha allele identified at DNA and protein level is strongly associated with celiac disease. Hum Immunol. 1988 Dec;23(4):271–279. doi: 10.1016/0198-8859(88)90062-6. [DOI] [PubMed] [Google Scholar]
  14. Ronchese F., Schwartz R. H., Germain R. N. Functionally distinct subsites on a class II major histocompatibility complex molecule. Nature. 1987 Sep 17;329(6136):254–256. doi: 10.1038/329254a0. [DOI] [PubMed] [Google Scholar]
  15. Sacks S. H., Bushell A., Rust N. A., Karagiannis J. A., Jewell D. P., Ledingham J. G., Wood K. J., McMichael A. J. Functional and biochemical subtypes of the haplotype HLA-DR3 in patients with celiac disease or idiopathic membranous nephropathy. Hum Immunol. 1987 Oct;20(2):175–187. doi: 10.1016/0198-8859(87)90031-0. [DOI] [PubMed] [Google Scholar]
  16. Saiki R. K., Bugawan T. L., Horn G. T., Mullis K. B., Erlich H. A. Analysis of enzymatically amplified beta-globin and HLA-DQ alpha DNA with allele-specific oligonucleotide probes. Nature. 1986 Nov 13;324(6093):163–166. doi: 10.1038/324163a0. [DOI] [PubMed] [Google Scholar]
  17. Saiki R. K., Gelfand D. H., Stoffel S., Scharf S. J., Higuchi R., Horn G. T., Mullis K. B., Erlich H. A. Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase. Science. 1988 Jan 29;239(4839):487–491. doi: 10.1126/science.2448875. [DOI] [PubMed] [Google Scholar]
  18. Scharf S. J., Horn G. T., Erlich H. A. Direct cloning and sequence analysis of enzymatically amplified genomic sequences. Science. 1986 Sep 5;233(4768):1076–1078. doi: 10.1126/science.3461561. [DOI] [PubMed] [Google Scholar]
  19. Sheldon E. L., Kellogg D. E., Watson R., Levenson C. H., Erlich H. A. Use of nonisotopic M13 probes for genetic analysis: application to HLA class II loci. Proc Natl Acad Sci U S A. 1986 Dec;83(23):9085–9089. doi: 10.1073/pnas.83.23.9085. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Sollid L. M., Markussen G., Ek J., Gjerde H., Vartdal F., Thorsby E. Evidence for a primary association of celiac disease to a particular HLA-DQ alpha/beta heterodimer. J Exp Med. 1989 Jan 1;169(1):345–350. doi: 10.1084/jem.169.1.345. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Southern E. M. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol. 1975 Nov 5;98(3):503–517. doi: 10.1016/s0022-2836(75)80083-0. [DOI] [PubMed] [Google Scholar]
  22. TERASAKI P. I., MCCLELLAND J. D. MICRODROPLET ASSAY OF HUMAN SERUM CYTOTOXINS. Nature. 1964 Dec 5;204:998–1000. doi: 10.1038/204998b0. [DOI] [PubMed] [Google Scholar]
  23. Todd J. A., Bell J. I., McDevitt H. O. HLA-DQ beta gene contributes to susceptibility and resistance to insulin-dependent diabetes mellitus. Nature. 1987 Oct 15;329(6140):599–604. doi: 10.1038/329599a0. [DOI] [PubMed] [Google Scholar]
  24. Tosi R., Tanigaki N., Polanco I., De Marchi M., Woodrow J. C., Hetzel P. A. A radioimmunoassay typing study of non-DQw2-associated celiac disease. Clin Immunol Immunopathol. 1986 Apr;39(1):168–172. doi: 10.1016/0090-1229(86)90216-3. [DOI] [PubMed] [Google Scholar]
  25. Tosi R., Vismara D., Tanigaki N., Ferrara G. B., Cicimarra F., Buffolano W., Follo D., Auricchio S. Evidence that celiac disease is primarily associated with a DC locus allelic specificity. Clin Immunol Immunopathol. 1983 Sep;28(3):395–404. doi: 10.1016/0090-1229(83)90106-x. [DOI] [PubMed] [Google Scholar]
  26. Weiss J. B., Austin R. K., Schanfield M. S., Kagnoff M. F. Gluten-sensitive enteropathy. Immunoglobulin G heavy-chain (Gm) allotypes and the immune response to wheat gliadin. J Clin Invest. 1983 Jul;72(1):96–101. doi: 10.1172/JCI110988. [DOI] [PMC free article] [PubMed] [Google Scholar]

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