{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T03:02:35Z","timestamp":1787022155389,"version":"build-2736575974"},"reference-count":35,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2024,7,18]],"date-time":"2024-07-18T00:00:00Z","timestamp":1721260800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Lamotrigine as a broad-spectrum antiepileptic drug, is widely applied and its clinical efficacy is highly recognized. However, significant differences are observed in blood drug concentration of lamotrigine among individuals, which may have an impact on its efficacy. UGT1A4 is the main metabolic enzyme. However, it was inconsistent for the influence of UGT1A4 genetic polymorphism on concentration and efficacy of lamotrigine therapy. This study aimed to evaluate the influences of UGT1A4*3 genetic polymorphisms on lamotrigine concentration and therapeutic effect through meta-analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The literature search was conducted in Medline, Embase, PubMed, Web of Science, Wan Fang Database, China National Knowledge Infrastructure, China Science and Technology Journal Database until January 2024. The primary outcome included the mean serum concentration, concentration-to-dose-ratio by body weight (CDR), or efficacy related to different UGT1A4*3 genotype for lamotrigine therapy. Data were collected to access the Mean Difference or odds ratio with 95% confidence interval. Meta-analysis was performed by RevMan 5.2.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A total of eleven studies were enrolled. The meta-analysis for mean serum concentration of lamotrigine showed no significant difference between patients carrying TT genotypes and TG and GG genotypes group (MD: 0.12, 95% [-0.35, 0.58],\n                      <jats:italic>P<\/jats:italic>\n                      = 0.62). There was significant difference in CDR (MD: 0.49, 95% [0.03, 0.94],\n                      <jats:italic>P<\/jats:italic>\n                      = 0.04) and therapeutic efficacy (OR: 7.18, 95% [4.01, 12.83],\n                      <jats:italic>P<\/jats:italic>\n                      &lt;0.00001) of lamotrigine, however no significant difference was found in subgroup analysis of CDR of children (MD: 0.03, 95% [-0.35, 0.42], P = 0.87) between patients carrying TT genotypes and TG and GG genotypes group.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Polymorphism of UGT1A4*3 influenced the CDR and therapeutic efficacy of lamotrigine for antiepileptic therapy. Genotype analysis provided reference for personalized medication in the future. However, more high-quality evidences are necessary for precise and definitive conclusion.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0307377","type":"journal-article","created":{"date-parts":[[2024,7,18]],"date-time":"2024-07-18T13:56:07Z","timestamp":1721310967000},"page":"e0307377","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":3,"title":["UGT1A4*3 polymorphism influences serum concentration and therapeutic effect of lamotrigine for epilepsy treatment: A meta-analysis"],"prefix":"10.1371","volume":"19","author":[{"given":"Zhimei","family":"Jiang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuzhi","family":"Fu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-8901-8033","authenticated-orcid":true,"given":"Hongxin","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,7,18]]},"reference":[{"issue":"10172","key":"pone.0307377.ref001","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1016\/S0140-6736(18)32596-0","article-title":"Epilepsy in adults","volume":"393","author":"D Thijs Roland","year":"2019","journal-title":"The Lancet"},{"issue":"4","key":"pone.0307377.ref002","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1111\/epi.13709","article-title":"ILAE classification of 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strategies","volume":"49","author":"PN Patsalos","year":"2008","journal-title":"Epilepsia"},{"key":"pone.0307377.ref012","first-page":"9","article-title":"AGNP consensus guidelines for therapeutic drug monitoring in psychiatry: update 2017","volume":"51","author":"C Hiemke","year":"2017","journal-title":"Pharmacopsychiatry"},{"issue":"4","key":"pone.0307377.ref013","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s00228-016-2190-2","article-title":"Population pharmacokinetic models of lamotrigine in different age groups of Chinese children with epilepsy","volume":"73","author":"ZB ZHANG","year":"2017","journal-title":"Eur J Clin Pharmacol"},{"issue":"8","key":"pone.0307377.ref014","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1016\/j.braindev.2016.03.004","article-title":"The effects of co-medications on lamotrigine clearance in Japanese children with epilepsy","volume":"38","author":"T TAKEUCHI","year":"2016","journal-title":"Brain 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Steady-State Serum Concentrations of Lamotrigine in Patients With Treatment-Resistant Depressive Disorder Receiving Lamotrigine as Augmentation Therapy","volume":"41","author":"Suzuki Takeshi","year":"2019","journal-title":"Ther Drug Monit"},{"key":"pone.0307377.ref022","doi-asserted-by":"crossref","first-page":"106897","DOI":"10.1016\/j.eplepsyres.2022.106897","article-title":"Effect of UGT1A4, UGT2B7, UGT2B15, UGT2B17 and ABC1B polymorphisms on lamotrigine metabolism in Danish patients","volume":"182","author":"Petrenaite Vaiva","year":"2022","journal-title":"Epilepsy Res"},{"issue":"1\u20132","key":"pone.0307377.ref023","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.eplepsyres.2011.01.016","article-title":"The relationship between UGT1A4 polymorphism and serum concentration of lamotrigine in patients with epilepsy","volume":"95","author":"Gulcebi Medine Idrizoglu","year":"2011","journal-title":"Epilepsy 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