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Review Article: The genetics of the human leucocyte antigen region in inflammatory bowel disease

Review Article: The genetics of the human leucocyte antigen region in inflammatory bowel disease
Review Article: The genetics of the human leucocyte antigen region in inflammatory bowel disease

Background

The human leucocyte antigen (HLA) complex, located at chromosome 6p21.3 is a highly polymorphic region containing the classical class I and II HLA genes. The region is highly associated with inflammatory bowel disease (IBD), largely through genome‐wide association studies (GWAS).
Aims

To review the role of HLA in immune function, summarise data on risk/protective HLA genotypes for IBD, discuss the role of HLA in IBD pathogenesis, treatment and examine limitations that might be addressed by future research.
Methods

An organised search strategy was used to collate articles describing HLA genes in IBD, including Crohn's disease and ulcerative colitis.
Results

All classical HLA genes with variation (including HLA‐A, B, C, DRB1, DQA1, DQB1, DPA1 and DPB1) harbour IBD‐associated genotypes. The most implicated gene is HLA‐DRB1, with HLA‐DRB1*03:01 the most associated risk allele in both Crohn's disease and ulcerative colitis. Elucidating precise disease associations is challenging due to high linkage disequilibrium between HLA genotypes. The mechanisms by which risk alleles cause disease are multifactorial, with the best evidence indicating structural and electrostatic alteration impacting antigen binding and downstream signalling. Adverse medication events have been associated with HLA genotypes including with thiopurines (pancreatitis) and anti‐TNF agents (antibody formation).
Conclusions

The HLA complex is associated with multiple risk/protective alleles for IBD. Future research utilising long‐read technology, ascertainment of zygosity and integration in disease modelling will improve the functional understanding and clinical translation of genetic findings.
0269-2813
885-900
Ashton, James, John
1c0bfa29-794c-4fd5-93e0-6769e6037d72
Latham, Katy
aa28dbc6-9b30-42e8-8f51-c681f4816f59
Beattie, R. Mark
55d81c7b-08c9-4f42-b6d3-245869badb71
Ennis, Sarah
7b57f188-9d91-4beb-b217-09856146f1e9
Ashton, James, John
1c0bfa29-794c-4fd5-93e0-6769e6037d72
Latham, Katy
aa28dbc6-9b30-42e8-8f51-c681f4816f59
Beattie, R. Mark
55d81c7b-08c9-4f42-b6d3-245869badb71
Ennis, Sarah
7b57f188-9d91-4beb-b217-09856146f1e9

Ashton, James, John, Latham, Katy, Beattie, R. Mark and Ennis, Sarah (2019) Review Article: The genetics of the human leucocyte antigen region in inflammatory bowel disease. Alimentary Pharmacology and Therapeutics, 50 (8), 885-900. (doi:10.1111/apt.15485).

Record type: Review

Abstract


Background

The human leucocyte antigen (HLA) complex, located at chromosome 6p21.3 is a highly polymorphic region containing the classical class I and II HLA genes. The region is highly associated with inflammatory bowel disease (IBD), largely through genome‐wide association studies (GWAS).
Aims

To review the role of HLA in immune function, summarise data on risk/protective HLA genotypes for IBD, discuss the role of HLA in IBD pathogenesis, treatment and examine limitations that might be addressed by future research.
Methods

An organised search strategy was used to collate articles describing HLA genes in IBD, including Crohn's disease and ulcerative colitis.
Results

All classical HLA genes with variation (including HLA‐A, B, C, DRB1, DQA1, DQB1, DPA1 and DPB1) harbour IBD‐associated genotypes. The most implicated gene is HLA‐DRB1, with HLA‐DRB1*03:01 the most associated risk allele in both Crohn's disease and ulcerative colitis. Elucidating precise disease associations is challenging due to high linkage disequilibrium between HLA genotypes. The mechanisms by which risk alleles cause disease are multifactorial, with the best evidence indicating structural and electrostatic alteration impacting antigen binding and downstream signalling. Adverse medication events have been associated with HLA genotypes including with thiopurines (pancreatitis) and anti‐TNF agents (antibody formation).
Conclusions

The HLA complex is associated with multiple risk/protective alleles for IBD. Future research utilising long‐read technology, ascertainment of zygosity and integration in disease modelling will improve the functional understanding and clinical translation of genetic findings.

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Clean_09_07_19_The Genetics of the HLA Region in Inflammatory Bowel Disease - Accepted Manuscript
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More information

Accepted/In Press date: 10 August 2019
e-pub ahead of print date: 13 September 2019
Published date: October 2019

Identifiers

Local EPrints ID: 433365
URI: http://eprints.soton.ac.uk/id/eprint/433365
ISSN: 0269-2813
PURE UUID: 3b9774a2-76d7-4945-9cb0-74895eecd7f9
ORCID for Sarah Ennis: ORCID iD orcid.org/0000-0003-2648-0869

Catalogue record

Date deposited: 15 Aug 2019 16:30
Last modified: 22 Nov 2021 07:36

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Contributors

Author: James, John Ashton
Author: Katy Latham
Author: R. Mark Beattie
Author: Sarah Ennis ORCID iD

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