{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T22:27:38Z","timestamp":1790288858284,"version":"4.1.0"},"reference-count":62,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2025,8,14]],"date-time":"2025-08-14T00:00:00Z","timestamp":1755129600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Minister of Health, Ricerca Corrente program 2025\u20132027"},{"name":"\u201c5 \u00d7 1000\u201d voluntary contribution"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Thiopurines are employed in inflammatory bowel diseases (IBDs; Crohn\u2019s disease, CD; ulcerative colitis, UC) to induce remission, prevent relapse, and reduce the steroid dosage, although they can sometimes be ineffective and present side effects. Genetic variations in the TPMT and NUDT15 genes are well recognized to influence the therapeutic response, despite notable regional differences in their frequencies across various ethnic populations. Herein, the risk haplotypes TPMT*3A, *3B, *3C, and the variant NUDT15*3 were examined in a retrospective cohort of 383 Italian IBD patients who received azathioprine or 6-mercaptopurine. TPMT and NUDT15 genotyping was performed by Sanger sequencing and TaqMan allelic discrimination, respectively. Allelic and genotype frequencies and genotype\u2013phenotype correlations in non-responder and intolerant patients were assessed in comparison to responders. In total, 17% of patients did not respond to treatment, while 20% experienced adverse events, with leukopenia found in 13% of patients. TPMT haplotypes were found in 3.1% of patients, and 1.6% had the NUDT15*3 variant. CD patients with leukopenia had a higher frequency of the TPMT risk haplotype (40% vs. 4%, p = 0.024). Although additional validation through larger prospective studies or meta-analyses is needed, our findings support the importance of TPMT gene-variant assessment for forecasting azathioprine-related leukopenia in Italian IBD patients.<\/jats:p>","DOI":"10.3390\/ijms26167860","type":"journal-article","created":{"date-parts":[[2025,8,14]],"date-time":"2025-08-14T15:44:21Z","timestamp":1755186261000},"page":"7860","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Examination of the TPMT and NUDT15*3 Variants to Predict the Response to Thiopurines in an Italian Cohort of Patients with Inflammatory Bowel Disease"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8831-7349","authenticated-orcid":false,"given":"Francesca","family":"Tavano","sequence":"first","affiliation":[{"name":"Division of Gastroenterology and Endoscopy, Fondazione IRCCS \u201cCasa Sollievo della Sofferenza\u201d, Viale Cappuccini 1, 71013 San Giovanni Rotondo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0019-7929","authenticated-orcid":false,"given":"Orazio","family":"Palmieri","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Endoscopy, Fondazione IRCCS \u201cCasa Sollievo della Sofferenza\u201d, Viale Cappuccini 1, 71013 San Giovanni Rotondo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Latiano","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Endoscopy, Fondazione IRCCS \u201cCasa Sollievo della Sofferenza\u201d, Viale Cappuccini 1, 71013 San Giovanni Rotondo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Domenica","family":"Gioffreda","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Endoscopy, Fondazione IRCCS \u201cCasa Sollievo della Sofferenza\u201d, Viale Cappuccini 1, 71013 San Giovanni Rotondo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiziana","family":"Latiano","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Endoscopy, Fondazione IRCCS \u201cCasa Sollievo della Sofferenza\u201d, Viale Cappuccini 1, 71013 San Giovanni Rotondo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Guerra","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Endoscopy, Fondazione IRCCS \u201cCasa Sollievo della Sofferenza\u201d, Viale Cappuccini 1, 71013 San Giovanni Rotondo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6053-3472","authenticated-orcid":false,"given":"Giuseppina","family":"Martino","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Endoscopy, Fondazione IRCCS \u201cCasa Sollievo della Sofferenza\u201d, Viale Cappuccini 1, 71013 San Giovanni Rotondo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4704-8354","authenticated-orcid":false,"given":"Maria Rosa","family":"Valvano","sequence":"additional","affiliation":[{"name":"Quality and Accreditation Unit, Fondazione IRCCS \u201cCasa Sollievo della Sofferenza\u201d, 71013 San Giovanni Rotondo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4518-9949","authenticated-orcid":false,"given":"Fabrizio","family":"Bossa","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Endoscopy, Fondazione IRCCS \u201cCasa Sollievo della Sofferenza\u201d, Viale Cappuccini 1, 71013 San Giovanni Rotondo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8314-8016","authenticated-orcid":false,"given":"Francesco","family":"Perri","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Endoscopy, Fondazione IRCCS \u201cCasa Sollievo della Sofferenza\u201d, Viale Cappuccini 1, 71013 San Giovanni Rotondo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Latiano","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Endoscopy, Fondazione IRCCS \u201cCasa Sollievo della Sofferenza\u201d, Viale Cappuccini 1, 71013 San Giovanni Rotondo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1590","DOI":"10.1016\/S0140-6736(12)60026-9","article-title":"Crohn\u2019s disease","volume":"380","author":"Baumgart","year":"2012","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1606","DOI":"10.1016\/S0140-6736(12)60150-0","article-title":"Ulcerative 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