HLA haplotypes in primary sclerosing cholangitis patients of admixed and non-European ancestry

E K K Henriksen; M K Viken; M Wittig; K Holm; T Folseraas; S Mucha; E Melum; J R Hov; K N Lazaridis; B D Juran; O Chazouillères; M Färkkilä; D N Gotthardt; P Invernizzi; M Carbone; G M Hirschfield; S M Rushbrook; E Goode; UK-PSC Consortium; C Y Ponsioen; R K Weersma; B Eksteen; K K Yimam; S C Gordon; D Goldberg; L Yu; C L Bowlus; A Franke; B A Lie; T H Karlsen

doi:10.1111/tan.13076

HLA haplotypes in primary sclerosing cholangitis patients of admixed and non-European ancestry

HLA. 2017 Oct;90(4):228-233. doi: 10.1111/tan.13076. Epub 2017 Jul 11.

Authors

E K K Henriksen^{1

2

3

4}, M K Viken^{3

5}, M Wittig⁶, K Holm^{1

2

3

4}, T Folseraas^{1

2

3

4

7}, S Mucha⁶, E Melum^{1

2

3

7}, J R Hov^{1

2

3

4

7}, K N Lazaridis⁸, B D Juran⁸, O Chazouillères⁹, M Färkkilä¹⁰, D N Gotthardt¹¹, P Invernizzi¹², M Carbone¹², G M Hirschfield¹³, S M Rushbrook¹⁴, E Goode¹⁵; UK-PSC Consortium; C Y Ponsioen¹⁶, R K Weersma¹⁷, B Eksteen¹⁸, K K Yimam¹⁹, S C Gordon²⁰, D Goldberg²¹, L Yu²², C L Bowlus²³, A Franke⁶, B A Lie^{3

5

24}, T H Karlsen^{1

2

3

4

7}

Affiliations

¹ Norwegian PSC Research Center, Department of Transplantation Medicine, Division of Surgery, Inflammatory Medicine and Transplantation, Oslo University Hospital Rikshospitalet, Oslo, Norway.
² Research Institute of Internal Medicine, Division of Surgery, Inflammatory Medicine and Transplantation, Oslo University Hospital Rikshospitalet, Oslo, Norway.
³ K.G. Jebsen Inflammation Research Centre, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
⁴ Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
⁵ Department of Immunology, Oslo University Hospital Rikshospitalet, Oslo, Norway.
⁶ Institute of Clinical Molecular Biology, Kiel University, Kiel, Germany.
⁷ Section of Gastroenterology, Department of Transplantation Medicine, Division of Surgery, Inflammatory Medicine and Transplantation, Oslo University Hospital Rikshospitalet, Oslo, Norway.
⁸ Center for Basic Research in Digestive Diseases, Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, Minnesota.
⁹ Hôpital Saint-Antoine, Service d'Hépatologie, INSERM, UMR_S 938, CDR Saint-Antoine, and Sorbonne Universités, UPMC Univ Paris 06, Paris, France.
¹⁰ Helsinki University and Clinic of Gastroenterology, Helsinki University Hospital, Helsinki, Finland.
¹¹ Department of Gastroenterology, Infectious Diseases and Intoxications, University Hospital of Heidelberg, Heidelberg, Germany.
¹² Program for Autoimmune Liver Diseases, International Center for Digestive Health, Department of Medicine and Surgery, University of Milan-Bicocca, Milan, Italy.
¹³ Centre for Liver Research and NIHR Birmingham Liver Biomedical Research Unit, Institute of Biomedical Research, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK.
¹⁴ The Department of Gastroenterology, Norfolk and Norwich University Hospitals NHS Foundation Trust, Norfolk, UK.
¹⁵ Wellcome Trust Sanger Institute, Hinxton and Institute of Metabolic Science, University of Cambridge, Cambridge, UK.
¹⁶ Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, the Netherlands.
¹⁷ Department of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
¹⁸ Snyder Institute for Chronic Diseases, Division of Gastroenterology, University of Calgary, Calgary, Canada.
¹⁹ Division of Hepatology and Liver Transplantation, California Pacific Medical Center, San Francisco, California.
²⁰ Division of Gastroenterology and Hepatology, Henry Ford Health System, Detroit, Michigan.
²¹ Division of Gastroenterology, Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
²² Department of Medicine, University of Washington, Seattle, Washington.
²³ Division of Gastroenterology and Hepatology, University of California Davis School of Medicine, Sacramento, California.
²⁴ Department of Medical Genetics, University of Oslo and Oslo University Hospital Ullevål, Oslo, Norway.

Abstract

Primary sclerosing cholangitis (PSC) is strongly associated with several human leukocyte antigen (HLA) haplotypes. Due to extensive linkage disequilibrium and multiple polymorphic candidate genes in the HLA complex, identifying the alleles responsible for these associations has proven difficult. We aimed to evaluate whether studying populations of admixed or non-European descent could help in defining the causative HLA alleles. When assessing haplotypes carrying HLA-DRB1*13:01 (hypothesized to specifically increase the susceptibility to chronic cholangitis), we observed that every haplotype in the Scandinavian PSC population carried HLA-DQB1*06:03. In contrast, only 65% of HLA-DRB1*13:01 haplotypes in an admixed/non-European PSC population carried this allele, suggesting that further assessments of the PSC-associated haplotype HLA-DRB1*13:01-DQA1*01:03-DQB1*06:03 in admixed or multi-ethnic populations could aid in identifying the causative allele.

Keywords: PSC; causative; human leukocyte antigen; multi-ethnic; trans-ancestry.

MeSH terms

Alleles
Cholangitis, Sclerosing / ethnology
Cholangitis, Sclerosing / genetics*
Cholangitis, Sclerosing / immunology
Ethnicity
Gene Expression
Gene Frequency
Genetic Predisposition to Disease*
HLA-DQ beta-Chains / classification
HLA-DQ beta-Chains / genetics*
HLA-DQ beta-Chains / immunology
HLA-DRB1 Chains / classification
HLA-DRB1 Chains / genetics*
HLA-DRB1 Chains / immunology
Haplotypes*
Humans
Linkage Disequilibrium
Scandinavian and Nordic Countries
White People

Substances

HLA-DQ beta-Chains
HLA-DQB1 antigen
HLA-DRB1 Chains

Grants and funding

R01 DK084960/DK/NIDDK NIH HHS/United States