Your browser doesn't support javascript.
loading
HLA-DQA1-HLA-DRB1 polymorphism is a major predictor of azathioprine-induced pancreatitis in patients with inflammatory bowel disease.
Wilson, A; Jansen, L E; Rose, R V; Gregor, J C; Ponich, T; Chande, N; Khanna, R; Yan, B; Jairath, V; Khanna, N; Sey, M; Beaton, M; McIntosh, K; Teft, W A; Kim, R B.
Afiliación
  • Wilson A; Division of Clinical Pharmacology, Department of Medicine, Western University, London, ON, Canada.
  • Jansen LE; Division of Gastroenterology, Department of Medicine, Western University, London, ON, Canada.
  • Rose RV; Department of Physiology and Pharmacology, Western University, London, ON, Canada.
  • Gregor JC; London Health Sciences Centre, London, ON, Canada.
  • Ponich T; Department of Epidemiology and Biostatistics, Western University, London, ON, Canada.
  • Chande N; Division of Gastroenterology, Department of Medicine, Western University, London, ON, Canada.
  • Khanna R; Division of Gastroenterology, Department of Medicine, Western University, London, ON, Canada.
  • Yan B; Division of Gastroenterology, Department of Medicine, Western University, London, ON, Canada.
  • Jairath V; Division of Gastroenterology, Department of Medicine, Western University, London, ON, Canada.
  • Khanna N; Division of Gastroenterology, Department of Medicine, Western University, London, ON, Canada.
  • Sey M; Division of Gastroenterology, Department of Medicine, Western University, London, ON, Canada.
  • Beaton M; Department of Epidemiology and Biostatistics, Western University, London, ON, Canada.
  • McIntosh K; Division of Gastroenterology, Department of Medicine, Western University, London, ON, Canada.
  • Teft WA; Division of Gastroenterology, Department of Medicine, Western University, London, ON, Canada.
  • Kim RB; Division of Gastroenterology, Department of Medicine, Western University, London, ON, Canada.
Aliment Pharmacol Ther ; 47(5): 615-620, 2018 03.
Article en En | MEDLINE | ID: mdl-29270995
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*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.
Asunto(s)
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Pancreatitis / Azatioprina / 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 Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Pancreatitis / Azatioprina / 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 Pais de publicación: Reino Unido