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

[1]  F. Carrat,et al.  Risk of Serious and Opportunistic Infections Associated With Treatment of Inflammatory Bowel Diseases. , 2018, Gastroenterology.

[2]  U. Hofmann,et al.  Preclinical evaluation of NUDT15-guided thiopurine therapy and its effects on toxicity and antileukemic efficacy. , 2018, Blood.

[3]  Y. Méndez,et al.  TPMT and NUDT15 genes are both related to mercaptopurine intolerance in acute lymphoblastic leukaemia patients from Uruguay , 2018, British journal of haematology.

[4]  M. Relling,et al.  Novel variants in NUDT15 and thiopurine intolerance in children with acute lymphoblastic leukemia from diverse ancestry. , 2017, Blood.

[5]  Motohiro Kato,et al.  The effects of inherited NUDT15 polymorphisms on thiopurine active metabolites in Japanese children with acute lymphoblastic leukemia , 2017, Pharmacogenetics and genomics.

[6]  Swarup A. V. Shah,et al.  Nucleoside diphosphate‐linked moiety X‐type motif 15 C415T variant as a predictor for thiopurine‐induced toxicity in Indian patients , 2017, Journal of gastroenterology and hepatology.

[7]  Xueding Wang,et al.  NUDT15 polymorphisms are better than thiopurine S‐methyltransferase as predictor of risk for thiopurine‐induced leukopenia in Chinese patients with Crohn's disease , 2016, Alimentary pharmacology & therapeutics.

[8]  Shane A. McCarthy,et al.  Reference-based phasing using the Haplotype Reference Consortium panel , 2016, Nature Genetics.

[9]  D. McGovern,et al.  Genetic variation in IBD: progress, clues to pathogenesis and possible clinical utility , 2016, Expert review of clinical immunology.

[10]  D. Gurwitz,et al.  Assessment of pharmacogenetic tests: presenting measures of clinical validity and potential population impact in association studies , 2016, The Pharmacogenomics Journal.

[11]  U. Hofmann,et al.  NUDT15 polymorphisms alter thiopurine metabolism and hematopoietic toxicity , 2016, Nature Genetics.

[12]  M. Tremelling,et al.  Clinical Features and HLA Association of 5-Aminosalicylate (5-ASA)-induced Nephrotoxicity in Inflammatory Bowel Disease. , 2016, Journal of Crohn's & colitis.

[13]  James Y. Zou Analysis of protein-coding genetic variation in 60,706 humans , 2015, Nature.

[14]  Gabor T. Marth,et al.  A global reference for human genetic variation , 2015, Nature.

[15]  Y. Kakuta,et al.  NUDT15 R139C causes thiopurine-induced early severe hair loss and leukopenia in Japanese patients with IBD , 2015, The Pharmacogenomics Journal.

[16]  R. Wade,et al.  Thiopurine methyltransferase and treatment outcome in the UK acute lymphoblastic leukaemia trial ALL2003 , 2015, British journal of haematology.

[17]  M. Relling,et al.  Inherited NUDT15 variant is a genetic determinant of mercaptopurine intolerance in children with acute lymphoblastic leukemia. , 2015, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[18]  M. Tremelling,et al.  HLA-DQA1–HLA-DRB1 variants confer susceptibility to pancreatitis induced by thiopurine immunosuppressants , 2014, Nature Genetics.

[19]  Jianjun Liu,et al.  A common missense variant in NUDT15 confers susceptibility to thiopurine-induced leukopenia , 2014, Nature Genetics.

[20]  Richard Durbin,et al.  Efficient haplotype matching and storage using the positional Burrows–Wheeler transform (PBWT) , 2014, Bioinform..

[21]  Iuliana Ionita-Laza,et al.  Sequence kernel association tests for the combined effect of rare and common variants. , 2013, American journal of human genetics.

[22]  J. Mate,et al.  Safety of Thiopurine Therapy in Inflammatory Bowel Disease: Long-term Follow-up Study of 3931 Patients , 2013, Inflammatory bowel diseases.

[23]  R. V. Schaik,et al.  A clinical approach to pharmacogenetics. , 2013 .

[24]  J. Miller,et al.  Predicting the Functional Effect of Amino Acid Substitutions and Indels , 2012, PloS one.

[25]  M. Pirmohamed,et al.  Development and Inter-Rater Reliability of the Liverpool Adverse Drug Reaction Causality Assessment Tool , 2011, PloS one.

[26]  O. Dewit,et al.  Limitations of extensive TPMT genotyping in the management of azathioprine-induced myelosuppression in IBD patients. , 2011, Clinical biochemistry.

[27]  P. Visscher,et al.  GCTA: a tool for genome-wide complex trait analysis. , 2011, American journal of human genetics.

[28]  Richard Durbin,et al.  Sequence analysis Fast and accurate short read alignment with Burrows – Wheeler transform , 2009 .

[29]  J. Gisbert,et al.  Thiopurine-Induced Myelotoxicity in Patients With Inflammatory Bowel Disease: A Review , 2008, The American Journal of Gastroenterology.

[30]  J. Satsangi,et al.  Toward an integrated clinical, molecular and serological classification of inflammatory bowel disease: report of a Working Party of the 2005 Montreal World Congress of Gastroenterology. , 2005, Canadian journal of gastroenterology = Journal canadien de gastroenterologie.

[31]  R. Gearry,et al.  Azathioprine and 6‐mercaptopurine pharmacogenetics and metabolite monitoring in inflammatory bowel disease , 2005, Journal of gastroenterology and hepatology.

[32]  D. Gaffney,et al.  Cost‐effectiveness of thiopurine methyltransferase genotype screening in patients about to commence azathioprine therapy for treatment of inflammatory bowel disease , 2004, Alimentary pharmacology & therapeutics.

[33]  P. J. Kelly,et al.  Inflammatory bowel disease: epidemiology and management in an English general practice population , 2000, Alimentary pharmacology & therapeutics.

[34]  B. Bonaz,et al.  Genotypic analysis of thiopurine S-methyltransferase in patients with Crohn's disease and severe myelosuppression during azathioprine therapy. , 2000, Gastroenterology.

[35]  U. Klotz,et al.  Thiopurine treatment in inflammatory bowel disease: clinical pharmacology and implication of pharmacogenetically guided dosing. , 2007, Clinical pharmacokinetics.