Dataset Information

A97 HLA-DQA1-HLA-DRB1 POLYMORPHISM IS A MAJOR PREDICTOR OF AZATHIOPRINE-INDUCED PANCREATITIS IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE

ABSTRACT: Abstract

Background

Azathioprine (AZA)-induced pancreatitis is an unpredictable and dose-independent adverse event affecting 2–7% of patients with inflammatory bowel disease (IBD) patients treated with AZA. There are no tools in clinical practice to identify at-risk individuals; however, a genome wide association study (GWAS) identified a strong association between the Class II HLA gene region polymorphism (rs2647087) and AZA-induced pancreatitis.

Aims

To independently confirm the findings of the GWAS in an IBD cohort, to evaluate its utility in clinical practice and to offer a novel AZA treatment algorithm for IBD based on pharmacogenomic principles.

Methods

A retrospective cohort study evaluated 373 AZA-exposed IBD patients from a tertiary care academic centre in London, Canada. All subjects underwent screening for the single nucleotide polymorphism (SNP) rs2647087 mapped to the HLA-DQA1*02:01-HLA-DRB1*07:01 haplotype and were sub-divided based on the presence (n = 13) or absence (n = 360) of an AZA-induced pancreatitis diagnosis. The risk of AZA-induced pancreatitis was assessed based on rs2647087 genotype.

Results

The risk of pancreatitis during AZA-therapy was highly predictable and genotype dependent: 0.53% for wild-type (A/A), 4.25% (OR=4.19, 95%CI 1.02–36.45, p=0.044) for heterozygous (A/C), and 14.63% (OR=15.83, 95%CI 3.80–145.26, p=0.0001) for homozygous variant (C/C) patients.

Conclusions

The class II HLA region (at rs2647087) is an important marker of AZA-induced pancreatitis risk. We propose a simple and clinically implementable algorithm based on rs2647087 and TPMT genotypes for AZA selection and dosing for patients with IBD. Genotype frequency stratified based on the presence or absence of pancreatitis. Genotypes are expressed as a percentage of the total population of the pancreatitis cases (n =13) and controls (n = 360).

Funding Agencies

CAG, CCC, CIHRCancer Care Ontario

SUBMITTER: Wilson A

PROVIDER: S-EPMC6508404 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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