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Recent studies have identified genetic <jats:italic>NUDT15<\/jats:italic> variants strongly associated with AZA\u2010induced leukopenia in Asian patients. This study aimed to investigate the strength of above genetic association and evaluate the usefulness of prospective screening of the <jats:italic>NUDT15<\/jats:italic> variants to prevent AZA\u2010induced leukopenia in Chinese patients. AZA\u2010induced leukopenia in patients with autoimmune disorders were enrolled from multiple medical centers in Taiwan\/China between 2012 and 2017 to determine the strength of genetic association of <jats:italic>NUDT15<\/jats:italic> or <jats:italic>TPMT<\/jats:italic> variants by whole exome sequencing (WES). Furthermore, a prospective study was conducted between 2018 and 2021 to investigate the incidence of AZA\u2010induced leukopenia with and without genetic screening. The WES result showed the genetic variants of <jats:italic>NUDT15 R139C<\/jats:italic> (<jats:italic>rs116855232<\/jats:italic>) (<jats:italic>P<\/jats:italic>\u00a0=\u00a03.7\u2009\u00d7\u200910<jats:sup>\u221225<\/jats:sup>, odds ratio (OR)\u00a0=\u00a021.7, 95% confidence interval (95% CI)\u00a0=\u00a012.1\u201338.8) and <jats:italic>NUDT15 rs746071566<\/jats:italic> (<jats:italic>P<\/jats:italic>\u00a0=\u00a04.2\u2009\u00d7\u200910<jats:sup>\u22129<\/jats:sup>, OR\u00a0=\u00a07.1, 95% CI\u00a0=\u00a03.7\u201313.7), but not <jats:italic>TPMT<\/jats:italic>, were associated with AZA\u2010induced leukopenia and <jats:italic>NUDT15 R139C<\/jats:italic> variant shows the highest sensitivity with 92.5%. Furthermore, the targeted screening of 1,013 participants for <jats:italic>NUDT15 R139C<\/jats:italic> enabled those identified as carriers to use alternative immunosuppressants. This strategy resulted in a significant decrease in the incidence of AZA\u2010induced leukopenia compared with historical incidence (incidence rate\u00a0=\u00a0from 7.6% decreased to 0.4%; <jats:italic>P<\/jats:italic>\u00a0=\u00a09.3\u2009\u00d7\u200910<jats:sup>\u221220<\/jats:sup>). In conclusion, the <jats:italic>NUDT15 R139C<\/jats:italic> variant was strongly associated with AZA\u2010induced leukopenia in Chinese patients. The genetic screening of <jats:italic>NUDT15 R139C<\/jats:italic> followed by use of alternative immunosuppressants in identified carriers effectively decreased the incidence of AZA leukopenia for patients with autoimmune disorders.<\/jats:p>","DOI":"10.1002\/cpt.2716","type":"journal-article","created":{"date-parts":[[2022,7,23]],"date-time":"2022-07-23T04:54:51Z","timestamp":1658552091000},"page":"1079-1087","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Implementation of <i>NUDT15<\/i> Genotyping to Prevent Azathioprine\u2010Induced Leukopenia for Patients With Autoimmune Disorders in Chinese Population"],"prefix":"10.1111","volume":"112","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7921-4129","authenticated-orcid":false,"given":"Chuang\u2010Wei","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Dermatology Drug Hypersensitivity Clinical and Research Center Chang Gung Memorial 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