{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T13:33:25Z","timestamp":1791812005546,"version":"4.3.4"},"reference-count":61,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2023,3,30]],"date-time":"2023-03-30T00:00:00Z","timestamp":1680134400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2023,8]]},"abstract":"<jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>\n                      Dihydropyrimidine dehydrogenase (DPD) deficiency can be detected by phenotyping (measurement of plasma uracil [U], with U\u2009\u2265\u200916\u2009\u03bcg\/L defining a partial deficiency) and\/or by genotyping (screening for the four most frequent\n                      <jats:italic>DPYD<\/jats:italic>\n                      variants). We aimed to determine the proportion of discrepancies between phenotypic and genotypic approaches and to identify possible explanatory factors.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Data from patients who underwent both phenotyping and genotyping were retrospectively collected. Complementary genetic analyses (genotyping of the variant c.557A&gt;G and\n                      <jats:italic>DPYD<\/jats:italic>\n                      sequencing) were performed for patients with U\u2009\u2265\u200916\u2009\u03bcg\/L without any common variants. The characteristics of patients classified according to the congruence of the phenotyping and genotyping approaches were compared (Kruskal\u2013Wallis test), and determinants of U levels were studied in the whole cohort (linear model).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Among the 712 included patients, phenotyping and genotyping were discordant for 12.5%, with 63 (8.8%) having U\u2009\u2265\u200916\u2009\u03bcg\/L in the absence of a common variant. Complementary genetic investigations marginally reduced the percentage of discrepancies to 12.1%: Among the nine additional identified variants, only the c.557A&gt;G variant, carried by three patients, had been previously reported to be associated with DPD deficiency. Liver dysfunction could explain certain discordances, as ASAT, ALP, GGT and bilirubin levels were significantly elevated, with more frequent liver metastases in patients with U\u2009\u2265\u200916\u2009\u03bcg\/L and the absence of a\n                      <jats:italic>DPYD<\/jats:italic>\n                      variant. The impact of cytolysis was confirmed, as ASAT levels were independently associated with increased U (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The frequent discordances between DPD phenotyping and genotyping approaches highlight the need to perform these two approaches to screen for all DPD deficiencies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bcp.15715","type":"journal-article","created":{"date-parts":[[2023,3,15]],"date-time":"2023-03-15T01:12:14Z","timestamp":1678842734000},"page":"2446-2457","source":"Crossref","is-referenced-by-count":10,"title":["Discrepancies between dihydropyrimidine dehydrogenase phenotyping and genotyping: What are the explanatory factors?"],"prefix":"10.1111","volume":"89","author":[{"given":"Capucine","family":"Arriv\u00e9","sequence":"first","affiliation":[{"name":"Univ. Grenoble Alpes, Laboratoire de Pharmacologie, Pharmacog\u00e9n\u00e9tique et Toxicologie CHU Grenoble Alpes  Grenoble France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xavier","family":"Fonrose","sequence":"additional","affiliation":[{"name":"Univ. Grenoble Alpes, Laboratoire de Pharmacologie, Pharmacog\u00e9n\u00e9tique et Toxicologie CHU Grenoble Alpes  Grenoble France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9886-412X","authenticated-orcid":false,"given":"Fabienne","family":"Thomas","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Institut Claudius\u2010Regaud, CRCT Universit\u00e9 de Toulouse, Inserm, UPS  Toulouse France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ga\u00ebl","family":"Roth","sequence":"additional","affiliation":[{"name":"Univ. Grenoble Alpes, Hepato\u2010Gastroenterology and Digestive Oncology Department, CHU Grenoble Alpes Institute for Advanced Biosciences  CNRS UMR 5309\u2010INSERM U1209 Grenoble France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuelle","family":"Jacquet","sequence":"additional","affiliation":[{"name":"Univ. Grenoble Alpes, Cancer and Blood Diseases Department, CHU Grenoble Alpes Institute for Advanced Biosciences  INSERM U1209 Grenoble France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aur\u00e9lie","family":"Brice","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Institut Claudius\u2010Regaud, CRCT Universit\u00e9 de Toulouse, Inserm, UPS  Toulouse France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carole","family":"Chirica","sequence":"additional","affiliation":[{"name":"Univ. Grenoble Alpes, Service de Biochimie, Biologie Mol\u00e9culaire et Toxicologie Environnementale CHU Grenoble\u2010Alpes  Grenoble France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Delphine","family":"Farneti","sequence":"additional","affiliation":[{"name":"Univ. Grenoble Alpes\/Cancer and Blood Diseases Department CHU Grenoble Alpes  Grenoble France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Coralie","family":"Frenoux","sequence":"additional","affiliation":[{"name":"Univ. Grenoble Alpes\/Cancer and Blood Diseases Department CHU Grenoble Alpes  Grenoble France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4643-6323","authenticated-orcid":false,"given":"Fran\u00e7oise","family":"Stanke\u2010Labesque","sequence":"additional","affiliation":[{"name":"Univ. Grenoble Alpes, Laboratoire de Pharmacologie, Pharmacog\u00e9n\u00e9tique et Toxicologie CHU Grenoble Alpes  Grenoble France"},{"name":"Univ. Grenoble Alpes, INSERM, CHU Grenoble Alpes, HP2  38000 Grenoble France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5846-3847","authenticated-orcid":false,"given":"Elodie","family":"Gautier\u2010Veyret","sequence":"additional","affiliation":[{"name":"Univ. Grenoble Alpes, Laboratoire de Pharmacologie, Pharmacog\u00e9n\u00e9tique et Toxicologie CHU Grenoble Alpes  Grenoble France"},{"name":"Univ. 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