{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T13:17:47Z","timestamp":1779110267602,"version":"3.51.4"},"reference-count":50,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2025,8,2]],"date-time":"2025-08-02T00:00:00Z","timestamp":1754092800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,8,2]],"date-time":"2025-08-02T00:00:00Z","timestamp":1754092800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100003453","name":"Natural Science Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2024A1515030299"],"award-info":[{"award-number":["2024A1515030299"]}],"id":[{"id":"10.13039\/501100003453","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      Adenosine, a purine nucleotide, is implicated in various brain disorders. Our previous study identified a correlation between\n                      <jats:italic>ADORA2A<\/jats:italic>\n                      variants and epilepsy susceptibility. However, it remains unclear whether\n                      <jats:italic>ADORA2A<\/jats:italic>\n                      genetic polymorphisms affect the outcomes of antiseizure medication (ASM) therapy. This study aimed to investigate the association between\n                      <jats:italic>ADORA2A<\/jats:italic>\n                      gene polymorphisms and the efficacy and adverse drug reactions (ADRs) of ASM.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      In this study, 278 children with epilepsy treated with ASM were retrospectively recruited. Among them, 208 children received valproic acid (VPA), 113 received oxcarbazepine (OXC), and 43 received a combination of VPA and OXC. The\n                      <jats:italic>ADORA2A<\/jats:italic>\n                      rs2298383 polymorphism was genotyped using the Sequenom MassArray system. Additionally, putative targets and pathways associated with\n                      <jats:italic>ADORA2A<\/jats:italic>\n                      in ADRs induced by ASM were identified through protein\u2013protein interaction, Kyoto Encyclopedia of Genes and Genomes, and Gene Ontology functional enrichment analysis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The\n                      <jats:italic>ADORA2A<\/jats:italic>\n                      rs2298383 polymorphism was not significantly associated with drug responsiveness in children with epilepsy. However, the rs2298383 TT genotype was potentially protective against VPA\u2010induced weight gain (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u2009.006) but may have increased the likelihood of OXC\u2010induced cutaneous ADRs (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u2009.030). Furthermore, bioinformatic analysis revealed that nine target genes associated with VPA\u2010induced weight gain were primarily involved in the \u201cpositive regulation of mitogen\u2010activated protein kinase cascade,\u201d \u201ccalcium signaling pathway,\u201d and \u201ccyclic adenosine monophosphate signaling pathway\u201d pathways\/processes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance<\/jats:title>\n                    <jats:p>\n                      This study demonstrates that\n                      <jats:italic>ADORA2A<\/jats:italic>\n                      gene polymorphisms can assist in predicting the impact of ASM on outcomes in children with epilepsy.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/epi.18587","type":"journal-article","created":{"date-parts":[[2025,8,2]],"date-time":"2025-08-02T15:29:47Z","timestamp":1754148587000},"page":"4725-4737","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Association study of\n                    <scp>\n                      <i>ADORA2A<\/i>\n                    <\/scp>\n                    gene polymorphisms with adverse drug reactions to valproic acid and oxcarbazepine in the treatment of children with epilepsy"],"prefix":"10.1111","volume":"66","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-2366-3214","authenticated-orcid":false,"given":"Xixuan","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Pharmacy, Shenzhen Baoan Women's and Children's Hospital Jinan University  Shenzhen China"},{"name":"Department of Clinical Pharmacology, College of Pharmacy Jinan University  Guangzhou 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