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.

Aliment Pharmacol Ther. 2019 Sep 13;:

Authors: Ashton JJ, Latham K, Beattie RM, Ennis S

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.

PMID: 31518029 [PubMed – as supplied by publisher]

PubMed Link: https://www.ncbi.nlm.nih.gov/pubmed/31518029?dopt=Abstract