{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T14:37:07Z","timestamp":1787841427039,"version":"build-2784847793"},"reference-count":12,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2024,5]]},"abstract":"Abstract:<\/jats:title>\n \n BACKGROUND:<\/jats:title>\n \n Azathioprine (AZA) is a widely used immunosuppressant drug. Leukopenia is a serious adverse effect of the drug which often necessitates dose reduction or drug withdrawal. Predictors of leukopenia include genetic and nongenetic factors. Genetic polymorphism of AZA-metabolizing enzyme, thiopurine S-methyltransferase (\n TPMT)<\/jats:italic>\n is well established. There is inconclusive evidence about the role of Nudix hydrolase (\n NUDT15)<\/jats:italic>\n gene polymorphism. This case\u2013control study assessed the association of genetic polymorphisms of\n NUDT15<\/jats:italic>\n and\n TPMT<\/jats:italic>\n with leukopenia induced by AZA.\n <\/jats:p>\n <\/jats:sec>\n \n MATERIALS AND METHODS:<\/jats:title>\n \n Cases were patients on AZA who developed leukopenia (white blood cell count <4000\/\u03bcl) within 1 year of treatment initiation that necessitated dose reduction or drug withdrawal. Age and gender-matched patients without leukopenia within 1 year of treatment with AZA served as controls.\n TPMT<\/jats:italic>\n (3 loci: c238G to C, c460G to A, c719A to G) and\n NUDT15<\/jats:italic>\n (c 415C to T, rs116855232) genotyping were done using TPMT strip assay and polymerase chain reaction\u2013restriction fragment length polymorphism, respectively. Genotype frequencies were noted, and the odds ratio was calculated to determine the association between genotypes and leukopenia.\n <\/jats:p>\n <\/jats:sec>\n \n RESULTS:<\/jats:title>\n \n Twenty-nine subjects (15 cases and 14 controls) were enrolled. Statistically significant differences were not observed in the TPMT genotype (*1\/*1 and *1\/*3C) (\n P<\/jats:italic>\n = 0.23) between cases and controls. NUDT15 genotypes (*1\/*1 and *1\/*3) (\n P<\/jats:italic>\n = 0.65) also showed no statistically significant difference between cases and controls.\n <\/jats:p>\n <\/jats:sec>\n \n CONCLUSION:<\/jats:title>\n The above genotypes do not appear to be associated with AZA-induced leukopenia in an eastern Indian population.<\/jats:p>\n <\/jats:sec>","DOI":"10.4103\/ijp.ijp_764_23","type":"journal-article","created":{"date-parts":[[2024,7,5]],"date-time":"2024-07-05T03:01:06Z","timestamp":1720148466000},"page":"166-171","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":3,"title":["Association of TPMT and NUDT15 gene polymorphisms with azathioprine-induced leukopenia: A case\u2013control study in Eastern India"],"prefix":"10.4103","volume":"56","author":[{"given":"Sneha","family":"Mitra","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Institute of Postgraduate Medical Education and Research, Kolkata, West Bengal, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abhijnan","family":"Ghosh","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Institute of Postgraduate Medical Education and Research, Kolkata, West Bengal, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suparna","family":"Chatterjee","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Institute of Postgraduate Medical Education and Research, Kolkata, West Bengal, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitali","family":"Chatterjee","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Institute of Postgraduate Medical Education and Research, Kolkata, West Bengal, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pradyot","family":"Sinhamahapatra","sequence":"additional","affiliation":[{"name":"Department of Clinical Immunology and Rheumatology, Institute of Postgraduate Medical Education and Research, Kolkata, West Bengal, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2024,7,5]]},"reference":[{"key":"R1-20240903","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1111\/j.1749-6632.1993.tb35896.x","article-title":"The George Hitchings and Gertrude Elion lecture. The pharmacology of azathioprine","volume":"685","author":"Elion","year":"1993","journal-title":"Ann N Y Acad Sci"},{"key":"R2-20240903","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1007\/s00228-007-0426-x","article-title":"Thiopurine S-methyltransferase activity in three major Asian populations: A population-based study in Singapore","volume":"64","author":"Kham","year":"2008","journal-title":"Eur J Clin Pharmacol"},{"key":"R3-20240903","doi-asserted-by":"crossref","first-page":"261","DOI":"10.15403\/jgld.2014.1121.252.nud","article-title":"NUDT15: A novel player in thiopurine metabolism","volume":"25","author":"Meijer","year":"2016","journal-title":"J Gastrointestin Liver Dis"},{"key":"R4-20240903","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.1038\/ng.3060","article-title":"Acommon missense variant in NUDT15 confers susceptibility to thiopurine-induced leukopenia","volume":"46","author":"Yang","year":"2014","journal-title":"Nat Genet"},{"key":"R5-20240903","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1038\/tpj.2015.43","article-title":"NUDT15 R139C causes thiopurine-induced early severe hair loss and leukopenia in Japanese patients with IBD","volume":"16","author":"Kakuta","year":"2016","journal-title":"Pharmacogenomics J"},{"key":"R7-20240903","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1089\/gtmb.2018.0313","article-title":"NUDT15 and TPMT genetic polymorphisms are related to azathioprine intolerance in Chinese patients with rheumatic diseases","volume":"23","author":"Yang","year":"2019","journal-title":"Genet Test Mol Biomarkers"},{"key":"R8-20240903","doi-asserted-by":"crossref","first-page":"27","DOI":"10.3390\/diagnostics7020027","article-title":"Comparison of direct sequencing, real-time PCR-High Resolution Melt (PCR-HRM) and PCR-restriction fragment length polymorphism (PCR-RFLP) analysis for genotyping of common thiopurine intolerant variant alleles NUDT15 c.415C>T and TPMT c.719A>G (TPMT*3C)","volume":"7","author":"Fong","year":"2017","journal-title":"Diagnostics (Basel)"},{"key":"R10-20240903","doi-asserted-by":"crossref","first-page":"460","DOI":"10.3389\/fphar.2018.00460","article-title":"NUDT15 R139C variants increase the risk of azathioprine-induced leukopenia in Chinese autoimmune patients","volume":"9","author":"Fei","year":"2018","journal-title":"Front Pharmacol"},{"key":"R12-20240903","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.1002\/cpt.1304","article-title":"Clinical pharmacogenetics implementation consortium guideline for thiopurine dosing based on TPMT and NUDT15 genotypes:2018 update","volume":"105","author":"Relling","year":"2019","journal-title":"Clin Pharmacol Ther"},{"key":"R13-20240903","doi-asserted-by":"crossref","first-page":"8309","DOI":"10.2147\/OTT.S177007","article-title":"Associations between the NUDT15 R139C polymorphism and susceptibility to thiopurine-induced leukopenia in Asians: A meta-analysis","volume":"11","author":"Liu","year":"2018","journal-title":"Onco Targets Ther"},{"key":"R14-20240903","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.phrs.2018.07.021","article-title":"Diagnostic accuracy of NUDT15 gene variants for thiopurine-induced leukopenia: A systematic review and meta-analysis","volume":"135","author":"Cargnin","year":"2018","journal-title":"Pharmacol Res"},{"key":"R15-20240903","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1002\/cpt.2716","article-title":"Implementation of NUDT15 genotyping to prevent azathioprine-induced leukopenia for patients with autoimmune disorders in Chinese population","volume":"112","author":"Wang","year":"2022","journal-title":"Clin Pharmacol Ther"}],"container-title":["Indian Journal of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ovid.com\/10.4103\/ijp.ijp_764_23","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T13:54:36Z","timestamp":1787838876000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/10.4103\/ijp.ijp_764_23"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5]]},"references-count":12,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2024]]}},"URL":"https:\/\/doi.org\/10.4103\/ijp.ijp_764_23","relation":{},"ISSN":["0253-7613","1998-3751"],"issn-type":[{"value":"0253-7613","type":"print"},{"value":"1998-3751","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5]]},"assertion":[{"value":"2023-11-24","name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-06-03","name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}}]}}