{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T22:46:05Z","timestamp":1761864365161,"version":"3.40.5"},"reference-count":27,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2021,12,4]],"date-time":"2021-12-04T00:00:00Z","timestamp":1638576000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Translational Sci"],"published-print":{"date-parts":[[2022,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Five\u2010fluorouracil (5\u2010FU) is a chemotherapeutic agent that is mainly metabolized by the rate\u2010limiting enzyme dihydropyrimidine dehydrogenase (DPD). The DPD enzyme activity deficiency involves a wide range of severities. Previous studies have demonstrated the effect of a <jats:italic>DPYD<\/jats:italic> single nucleotide polymorphism on 5\u2010FU efficacy and highlighted the importance of studying such genes for cancer treatment. Common polymorphisms of <jats:italic>DPYD<\/jats:italic> in European ancestry populations are less frequently present in Koreans. DPD is also responsible for the conversion of endogenous uracil (U) into dihydrouracil (DHU). We quantified U and DHU in plasma samples of healthy male Korean subjects, and samples were classified into two groups based on DHU\/U ratio. The calculated DHU\/U ratios ranged from 0.52 to 7.12, and the two groups were classified into the 10th percentile and 90th percentile for untargeted metabolomics analysis using liquid chromatography\u2010quantitative time\u2010of\u2010flight\u2010mass spectrometry. A total of 4440 compounds were detected and filtered out based on a coefficient of variation below 30%. Our results revealed that six metabolites differed significantly between the high activity group and low activity group (false discovery rate <jats:italic>q<\/jats:italic>\u2010value &lt; 0.05). Uridine was significantly higher in the low DPD activity group and is a precursor of U involved in pyrimidine metabolism; therefore, we speculated that DPD deficiency can influence uridine levels in plasma. Furthermore, the cutoff values for detecting DPD deficient patients from previous studies were unsuitable for Koreans. Our metabolomics approach is the first study that reported the DHU\/U ratio distribution in healthy Korean subjects and identified a new biomarker of DPD deficiency.<\/jats:p>","DOI":"10.1111\/cts.13203","type":"journal-article","created":{"date-parts":[[2021,12,4]],"date-time":"2021-12-04T18:08:55Z","timestamp":1638641335000},"page":"1104-1111","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Endogenous metabolic markers for predicting the activity of dihydropyrimidine dehydrogenase"],"prefix":"10.1111","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4435-6864","authenticated-orcid":false,"given":"Jihyun","family":"Kang","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacology and Therapeutics Seoul National University College of Medicine and Hospital  Seoul Korea"},{"name":"Department of Biomedical Sciences Seoul National University College of Medicine  Seoul Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0971-6024","authenticated-orcid":false,"given":"Andrew HyoungJin","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Medicine Division of Infectious Diseases Washington University School of Medicine  St. Louis Missouri USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4035-1230","authenticated-orcid":false,"given":"Inseung","family":"Jeon","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology and Therapeutics Seoul National University College of Medicine and Hospital  Seoul Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6275-8587","authenticated-orcid":false,"given":"Jaeseong","family":"Oh","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology and Therapeutics Seoul National University College of Medicine and Hospital  Seoul Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8384-3139","authenticated-orcid":false,"given":"In\u2010Jin","family":"Jang","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology and Therapeutics Seoul National University College of Medicine and Hospital  Seoul Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1713-9194","authenticated-orcid":false,"given":"SeungHwan","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology and Therapeutics Seoul National University College of Medicine and Hospital  Seoul Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9270-8273","authenticated-orcid":false,"given":"Joo\u2010Youn","family":"Cho","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology and Therapeutics 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