The risk of azathioprine-induced pancreatitis depends on genetic variants in the HLA gene region

Abstract

Introduction Acute pancreatitis occurs in around 2% of inflammatory bowel disease patients exposed to azathioprine or 6-mercaptopurine and is an important limiting toxicity of these thiopurine antimetabolites. Factors determining the risk of pancreatitis are unknown: the risk is not related to dose, though it may occur more commonly in individuals with Crohn's disease than in other disorders. Recently genome-wide association studies (GWASs) identified common genetic variants conferring substantial effects on risk for other idiosyncratic drug reactions (SCOL1B variants in simvastatin-induced myopathy and HLA-B5701 in flucloxacillin-induced liver injury). We hypothesised that the risk of pancreatitis was similarly determined by unknown common genetic variants of large effect size and that such variants might enable stratification of individuals for pancreatitis risk prior to commencing thiopurine therapy.