Collagenous Colitis Is Associated With HLA Signature and Shares Genetic Risks With Other Immune-Mediated Diseases.

Autor:	Stahl E; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York., Roda G; Inflammatory Bowel Diseases Center, Humanitas Research Hospital, Milan, Italy., Dobbyn A; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York., Hu J; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York., Zhang Z; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York., Westerlind H; Department of Medicine, Karolinska Institutet, Stockholm, Sweden., Bonfiglio F; Department of Medicine, Karolinska Institutet, Stockholm, Sweden., Raj T; Ronald M. Loeb Center for Alzheimer's Disease, Departments of Neuroscience, and Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York., Torres J; Department of Gastroenterology, Hospital Beatriz Angelo, Loures, Portugal., Chen A; Department of Pathology, Icahn School of Medicine, New York, New York., Petras R; AmeriPath Institute of Gastrointestinal Pathology and Digestive Disease, Cleveland, Ohio., Pardi DS; Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota., Iuga AC; Department of Biology and Cell Pathology, Columbia University, New York, New York., Levi GS; Department of Pathology, Icahn School of Medicine, New York, New York., Cao W; Division of Anatomic Pathology, New York University Langone Medical Center, New York, New York., Jain P; Department of Hematology and Oncology, University Hospitals, Case Comprehensive Cancer Center, Cleveland, Ohio., Rieder F; Department of Pathology, Robert J. Tomsich Pathology and Laboratory Medicine Institute, Cleveland Clinic, Cleveland, Ohio., Gordon IO; Department of Pathology, Robert J. Tomsich Pathology and Laboratory Medicine Institute, Cleveland Clinic, Cleveland, Ohio., Cho JH; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York., D'Amato M; Department of Medicine, Karolinska Institutet, Stockholm, Sweden; School of Biological Sciences, Monash University, Clayton, Victoria, Australia., Harpaz N; Department of Pathology, Icahn School of Medicine, New York, New York., Hao K; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York., Colombel JF; The Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York. Electronic address: jean-frederic.colombel@mssm.edu., Peter I; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York.
Jazyk:	angličtina
Zdroj:	Gastroenterology [Gastroenterology] 2020 Aug; Vol. 159 (2), pp. 549-561.e8. Date of Electronic Publication: 2020 May 01.
DOI:	10.1053/j.gastro.2020.04.063
Abstrakt:	Background & Aims: Collagenous colitis (CC) is an inflammatory bowel disorder with unknown etiopathogenesis involving HLA-related immune-mediated responses and environmental and genetic risk factors. We carried out an array-based genetic association study in a cohort of patients with CC and investigated the common genetic basis between CC and Crohn's disease (CD), ulcerative colitis (UC), and celiac disease. Methods: DNA from 804 CC formalin-fixed, paraffin-embedded tissue samples was genotyped with Illumina Immunochip. Matching genotype data on control samples and CD, UC, and celiac disease cases were provided by the respective consortia. A discovery association study followed by meta-analysis with an independent cohort, polygenic risk score calculation, and cross-phenotype analyses were performed. Enrichment of regulatory expression quantitative trait loci among the CC variants was assessed in hemopoietic and intestinal cells. Results: Three HLA alleles (HLA-B∗08:01, HLA-DRB1∗03:01, and HLA-DQB1∗02:01), related to the ancestral haplotype 8.1, were significantly associated with increased CC risk. We also identified an independent protective effect of HLA-DRB1∗04:01 on CC risk. Polygenic risk score quantifying the risk across multiple susceptibility loci was strongly associated with CC risk. An enrichment of expression quantitative trait loci was detected among the CC-susceptibility variants in various cell types. The cross-phenotype analysis identified a complex pattern of polygenic pleiotropy between CC and other immune-mediated diseases. Conclusions: In this largest genetic study of CC to date with histologically confirmed diagnosis, we strongly implicated the HLA locus and proposed potential non-HLA mechanisms in disease pathogenesis. We also detected a shared genetic risk between CC, celiac disease, CD, and UC, which supports clinical observations of comorbidity. (Copyright © 2020 AGA Institute. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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