Association of Genetic Variants in NUDT15 with Thiopurine-Induced
Research JAMA | Original Investigation AssociationofGeneticVariantsinNUDT15WithThiopurine-Induced Myelosuppression in Patients With Inflammatory Bowel Disease Gareth J. Walker, MBBS; James W. Harrison, PhD; Graham A. Heap, PhD; Michiel D. Voskuil, MD; Vibeke Andersen, MD; Carl A. Anderson, PhD; Ashwin N. Ananthakrishnan, MD; Jeffrey C. Barrett, PhD; Laurent Beaugerie, PhD; Claire M. Bewshea, MSc; Andy T. Cole, DM; Fraser R. Cummings, DPhil; Mark J. Daly, PhD; Pierre Ellul, PhD; Richard N. Fedorak, MD; Eleonora A. M. Festen, MD; Timothy H. Florin, MBBS; Daniel R. Gaya, DM; Jonas Halfvarson, MD; Ailsa L. Hart, PhD; Neel M. Heerasing, MBBS; Peter Hendy, MBBS; Peter M. Irving, MD; Samuel E. Jones, PhD; Jukka Koskela, MD; James O. Lindsay, PhD; John C. Mansfield, MD; Dermot McGovern, DPhil; Miles Parkes, DM; Richard C. G. Pollok, PhD; Subramaniam Ramakrishnan, MD; David S. Rampton, DPhil; Manuel A. Rivas, DPhil; Richard K. Russell, PhD; Michael Schultz, PhD; Shaji Sebastian, MD; Philippe Seksik, PhD; Abhey Singh, MBBS; Kenji So, MBBS; Harry Sokol, PhD; Kavitha Subramaniam, MBBS; Anthony Todd, MBChB; Vito Annese, MD; Rinse K. Weersma, MD; Ramnik Xavier, MD; Rebecca Ward, MSc; Michael N. Weedon, PhD; James R. Goodhand, MBBS; Nicholas A. Kennedy, MBBS; Tariq Ahmad, DPhil; for the IBD Pharmacogenetics Study Group Supplemental content IMPORTANCE Use of thiopurines may be limited by myelosuppression. TPMT pharmacogenetic testing identifies only 25% of at-risk patients of European ancestry. Among patients of East Asian ancestry, NUDT15 variants are associated with thiopurine-induced myelosuppression (TIM). OBJECTIVE To identify genetic variants associated with TIM among patients of European ancestry with inflammatory bowel disease (IBD). DESIGN, SETTING, AND PARTICIPANTS Case-control study of 491 patients affected by TIM and 679 thiopurine-tolerant unaffected patients who were recruited from 89 international sites between March 2012 and November 2015.
[Show full text]