HLA-DQA1-HLA-DRB1 polymorphism is a major predictor of azathioprine-induced pancreatitis in patients with inflammatory bowel disease.
Aliment Pharmacol Ther
; 47(5): 615-620, 2018 03.
Article
en En
| MEDLINE
| ID: mdl-29270995
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 thiopurine-induced pancreatitis.AIM:
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. Due to the limited number of patients taking mercaptopurine (MP), such patients were not included this cohort. All subjects underwent screening for the single nucleotide polymorphism (SNP) rs2647087 mapped to the HLA-DQA1*0201-HLA-DRB1*0701 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.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Pancreatitis
/
Azatioprina
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Enfermedades Inflamatorias del Intestino
/
Cadenas alfa de HLA-DQ
/
Cadenas HLA-DRB1
Tipo de estudio:
Etiology_studies
/
Incidence_studies
/
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Límite:
Adult
/
Female
/
Humans
/
Male
/
Middle aged
País/Región como asunto:
America do norte
Idioma:
En
Revista:
Aliment Pharmacol Ther
Asunto de la revista:
FARMACOLOGIA
/
GASTROENTEROLOGIA
/
TERAPIA POR MEDICAMENTOS
Año:
2018
Tipo del documento:
Article
País de afiliación:
Canadá