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Article has an altmetric score of 6

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Referenced in 21 patents
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Research Article Free access | 10.1172/JCI116613

Ulcerative colitis: a genetically heterogeneous disorder defined by genetic (HLA class II) and subclinical (antineutrophil cytoplasmic antibodies) markers.

H Yang, J I Rotter, H Toyoda, C Landers, D Tyran, C K McElree, and S R Targan

Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048.

Find articles by Yang, H. in: JCI | PubMed | Google Scholar

Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048.

Find articles by Rotter, J. in: JCI | PubMed | Google Scholar

Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048.

Find articles by Toyoda, H. in: JCI | PubMed | Google Scholar

Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048.

Find articles by Landers, C. in: JCI | PubMed | Google Scholar

Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048.

Find articles by Tyran, D. in: JCI | PubMed | Google Scholar

Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048.

Find articles by McElree, C. in: JCI | PubMed | Google Scholar

Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048.

Find articles by Targan, S. in: JCI | PubMed | Google Scholar

Published August 1, 1993 - More info

Published in Volume 92, Issue 2 on August 1, 1993
J Clin Invest. 1993;92(2):1080–1084. https://doi.org/10.1172/JCI116613.
© 1993 The American Society for Clinical Investigation
Published August 1, 1993 - Version history
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Abstract

Newly described distinct associations of HLA class II genes with ulcerative colitis (UC) (DR2) and Crohn's disease (CD) (DR1/DQ5) provide strong evidence for genetic heterogeneity of susceptibility between these two forms of inflammatory bowel disease. A familial distribution of antineutrophil cytoplasmic antibodies (ANCAs, a subclinical marker of UC) in UC families has further implied the existence of heterogeneity within UC. To test the hypothesis that the heterogeneity within UC indicated by ANCAs has a genetic basis that resides within the HLA region, we studied 89 UC cases and an ethnically matched control group (n = 50). Serological and molecular typing techniques were applied to define HLA class II genes (DR, DQ). ANCAs were detected using an enzyme-linked immunosorbent assay, and positive values were confirmed by indirect immunofluorescence. We observed that ANCA-positive UC patients (n = 70) had a significantly increased frequency of DR2 compared with ANCA-negative controls (n = 46) (44% vs 22%, P = 0.01). In contrast, the frequency of DR2 in ANCA-negative UC cases (21%) was virtually identical to that in controls (22%, P = 0.9). Furthermore, the ANCA-negative UC patients had an increase in the DR4 allele compared with ANCA-positive UC (P = 0.004). Thus, with the combination of a subclinical marker (ANCAs) and molecular genetic markers, genetic heterogeneity has been demonstrated within UC: ANCA-positive UC associated with DR2, and ANCA-negative UC likely associated with DR4.

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Referenced in 21 patents
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