Sequential evaluation of thiopurine methyltransferase, inosine triphosphate pyrophosphatase, and HPRT1 genes polymorphisms to explain thiopurines' toxicity and efficacy

Summary Aim To evaluate the polymorphisms of several genes involved in the azathioprine and mercaptopurine metabolism, in an attempt to explain their toxicity and efficacy in Crohn’s disease and ulcerative colitis. Methods In 422 consecutive patients (250 with Crohn’s disease and 172 with ulcerative colitis) and 245 healthy controls, single nucleotide polymorphisms of thiopurine methyltransferase, inosine triphosphate pyrophosphatase and hypoxanthine phosphoribosyl transferase (HPRT1) genes were related to the occurrence of adverse drug reactions (ADRs) and efficacy of therapy. Results Seventy‐three patients reported 81 episodes of ADRs; 45 patients did not respond to therapy. Frequency of thiopurine methyltransferase risk haplotypes was significantly increased in patients with leucopenia (26% vs. 5.7% in patients without ADRs, and 4% of controls) (P