ArticleClinical pharmacology and therapeutics2025
RAB19, SERPINB9P1, and Pancreatitis in Patients Taking Azathioprine in Routine Clinical Practice: Genome and Transcriptome-Wide Association Studies.
Article in Clinical pharmacology and therapeutics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Azathioprine is used to treat several inflammatory and autoimmune diseases. However, its use is limited by serious adverse events, including acute pancreatitis. Prior studies have found an association between the HLA region and thiopurine-induced acute pancreatitis (TIAP); however, in clinical practice, many patients with pancreatitis do not meet this strict criterion. We aimed to identify additional genes associated with azathioprine-related pancreatitis using genome-wide and transcriptome-wide association studies (GWAS and TWAS) by broadening the definition of pancreatitis. We conducted a retrospective study of azathioprine users with inflammatory conditions. We used electronic health records linked to genomic data from BioVU (Vanderbilt's biobank) and replicated the results using NIH's All of Us. The primary outcome was acute pancreatitis, and the secondary outcome was pancreatic injury. Sixteen patients with pancreatitis and 2085 control subjects were included from BioVU; the All of Us cohort included < 20 patients with pancreatitis and 847 control subjects. The GWAS analysis (adjusted for 10 principal components of genetic ancestry, sex, age, and azathioprine indication) in the BioVU cohort found an association between pancreatic injury and rs2948386 in RAB19 (OR = 3.47, P = 1.46E
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