{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T17:25:33Z","timestamp":1771262733953,"version":"3.50.1"},"reference-count":34,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T00:00:00Z","timestamp":1761523200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T00:00:00Z","timestamp":1761523200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100009367","name":"Mansoura University","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100009367","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Eur J Med Res"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>\n                      The\n                      <jats:italic>GABRG2<\/jats:italic>\n                      gene polymorphisms C588T and 3145G&gt;A could be predictive genetic markers that trigger idiopathic generalized epilepsy (IGE) or predict pharmaco-resistance to antiseizure medications (ASMs).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      This case\u2012control study enrolled 85 children, including 34 patients with IGE who were responsive to ASMs (responsive group), 30 patients with IGE who were resistant to ASMs (resistant group), and 21 healthy children (control group). All participants were assessed for the\n                      <jats:italic>GABRG2<\/jats:italic>\n                      C588T and\n                      <jats:italic>GABRG2<\/jats:italic>\n                      3145G&gt;A gene polymorphisms via polymerase chain reaction (PCR).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The CC genotype of the\n                      <jats:italic>GABRG2<\/jats:italic>\n                      polymorphism was the most commonly reported genotype. The CT and TT genotypes were more frequently associated with epileptic patients than with controls. The T allele and the T-included genotypes were more common among epileptic patients than controls. Regarding the\n                      <jats:italic>GABRG2<\/jats:italic>\n                      _3145G&gt;A polymorphism, the AG genotype was the most frequent among the study groups. The GG phenotype was more common among epileptic children than in controls. The G allele and G-included genotypes were significantly associated with epilepsy (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.02), with a 3.2-fold higher risk of occurrence of epilepsy for the G allele carriers. A statistically insignificant difference in the distribution of different genotypes and C &amp; T alleles of the\n                      <jats:italic>GABRG2<\/jats:italic>\n                      C588T polymorphism was detected between the ASMs-responsive and the ASMs-resistant subgroups. However, the TT genotype was more common in the ASMs-resistant subgroup (10% vs. 3%). The\n                      <jats:italic>GABRG2<\/jats:italic>\n                      _3145G&gt;A polymorphism appeared to be a prognostic determinant of ASMs responsiveness; the GG genotype was significantly associated with poor control of seizure activity (47% vs. 24%,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.05). The G-included genotypes were significantly associated with ASMs resistance (76% vs. 53%,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.05).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      The T allele and TT genotype of the\n                      <jats:italic>GABRG2<\/jats:italic>\n                      C588T gene were more common among patients with IGE, whereas the G allele and the GG genotype of the\n                      <jats:italic>GABRG2<\/jats:italic>\n                      3145G&gt;A gene may be significant predictors of ASMs resistance among IGE patients. Results validation in larger, multi-center studies across diverse populations is recommended.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s40001-025-03230-x","type":"journal-article","created":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T08:06:26Z","timestamp":1761552386000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Association of GABRG2 gene polymorphisms with idiopathic generalized epilepsy in Egyptian children: a case\u2013control study"],"prefix":"10.1186","volume":"30","author":[{"given":"Yahya","family":"Wahba","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Doaa","family":"Shahin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abdel-Hady","family":"El-Gilany","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sohier","family":"Yahia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nora","family":"El-Tantawy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohamed","family":"Khodair","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hanan","family":"Sherbiny","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hanaa","family":"Khalil","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Khadeja","family":"Soheeb","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,10,27]]},"reference":[{"key":"3230_CR1","doi-asserted-by":"publisher","first-page":"771","DOI":"10.1186\/s12889-024-18236-z","volume":"24","author":"G Biset","year":"2024","unstructured":"Biset G, Abebaw N, Gebeyehu NA, Estifanos N, Birrie E, Tegegne KD. Prevalence, incidence, and trends of epilepsy among children and adolescents in Africa: a systematic review and meta-analysis. BMC Public Health. 2024;24:771.","journal-title":"BMC Public Health"},{"key":"3230_CR2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000208076","volume":"102","author":"O Devinsky","year":"2024","unstructured":"Devinsky O, Elder C, Sivathamboo S, Scheffer IE, Koepp MJ. Idiopathic generalized epilepsy: misunderstandings, challenges, and opportunities. Neurology. 2024;102:e208076.","journal-title":"Neurology"},{"key":"3230_CR3","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1111\/j.1528-1167.2010.02848.x","volume":"51","author":"P Cossette","year":"2010","unstructured":"Cossette P, Rouleau GA. Mutated GABAA receptor subunits in idiopathic generalized epilepsy. Epilepsia. 2010;51:62\u201362.","journal-title":"Epilepsia"},{"key":"3230_CR4","doi-asserted-by":"publisher","first-page":"550","DOI":"10.1089\/gtmb.2011.0225","volume":"16","author":"S Ponnala","year":"2012","unstructured":"Ponnala S, Chaudhari JR, Jaleel MA, Bhiladvala D, Kaipa PR, Das UN, et al. Role of MDR1 C3435T and GABRG2 C588T gene polymorphisms in seizure occurrence and MDR1 effect on anti-epileptic drug (phenytoin) absorption. Genet Test Mol Biomarkers. 2012;16:550\u20137.","journal-title":"Genet Test Mol Biomarkers"},{"key":"3230_CR5","doi-asserted-by":"publisher","first-page":"605","DOI":"10.1097\/FPC.0000000000000000","volume":"23","author":"S Balan","year":"2013","unstructured":"Balan S, Sathyan S, Radha SK, Joseph V, Radhakrishnan K, Banerjee M. GABRG2, rs211037 is associated with epilepsy susceptibility, but not with antiepileptic drug resistance and febrile seizures. Pharmacogenet Genomics. 2013;23:605\u201310.","journal-title":"Pharmacogenet Genomics"},{"key":"3230_CR6","doi-asserted-by":"crossref","unstructured":"Haerian BS, Baum L, Kwan P, Cherny SS, Shin J-G, Kim SE, et al. Contribution of GABRG2 polymorphisms to risk of epilepsy and febrile seizure: \na multicenter cohort study and meta-analysis. Mol. Neurobiol. 2016;53:5457\u20135467","DOI":"10.1007\/s12035-015-9457-y"},{"key":"3230_CR7","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1007\/s13295-013-0040-6","volume":"4","author":"U Hedrich","year":"2013","unstructured":"Hedrich U, Maljevic S, Lerche H. Mechanisms of genetic epilepsies. e-Neuroforum. 2013;4:23\u201330.","journal-title":"e-Neuroforum"},{"key":"3230_CR8","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2022.809163","volume":"15","author":"Y Yang","year":"2022","unstructured":"Yang Y, Niu X, Cheng M, Zeng Q, Deng J, Tian X, et al. Phenotypic spectrum and prognosis of epilepsy patients with GABRG2 variants. Front Mol Neurosci. 2022;15:809163.","journal-title":"Front Mol Neurosci"},{"key":"3230_CR9","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1007\/s12031-018-1081-7","volume":"65","author":"MA Bhat","year":"2018","unstructured":"Bhat MA, Guru SA, Mir R, Waza AA, Zuberi M, Sumi MP, et al. Association of GABAA receptor gene with epilepsy syndromes. J Mol Neurosci. 2018;65:141\u201353.","journal-title":"J Mol Neurosci"},{"key":"3230_CR10","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1007\/s12031-018-1081-7","volume":"65","author":"MA Bhat","year":"2018","unstructured":"Bhat MA, Guru SA, Mir R, Waza AA, Zuberi M, Sumi MP, et al. Association of GABAA receptor gene with epilepsy syndromes. J Mol Neurosci. 2018;65:141\u201353.","journal-title":"J Mol Neurosci"},{"key":"3230_CR11","doi-asserted-by":"publisher","first-page":"442","DOI":"10.1016\/S1044-7431(03)00202-1","volume":"24","author":"C Schweizer","year":"2003","unstructured":"Schweizer C, Balsiger S, Bluethmann H, Mansuy IM, Fritschy J-M, Mohler H, et al. The \u03b32 subunit of GABAA receptors is required for maintenance of receptors at mature synapses. Mol Cell Neurosci. 2003;24:442\u201350.","journal-title":"Mol Cell Neurosci"},{"key":"3230_CR12","doi-asserted-by":"publisher","first-page":"1725","DOI":"10.1111\/cts.12997","volume":"14","author":"S Wang","year":"2021","unstructured":"Wang S, Zhang X, Zhou L, Wu Q, Han Y. Analysis of GABRG2 C588T polymorphism in genetic epilepsy and evaluation of GABRG2 in drug treatment. Clin Transl Sci. 2021;14:1725\u201333.","journal-title":"Clin Transl Sci"},{"key":"3230_CR13","doi-asserted-by":"crossref","unstructured":"Rossi A, Lin SX, Absalom NL, Ortiz-De la Rosa S, Liao VW, Mohammadi NA, et al. Phenotypic Spectrum in Individuals With Pathogenic GABRG2 Loss- and Gain-of-Function Variants. Neurol. 2025;105(2):e213644","DOI":"10.1212\/WNL.0000000000213644"},{"key":"3230_CR14","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1016\/j.pediatrneurol.2006.09.011","volume":"36","author":"I-C Chou","year":"2007","unstructured":"Chou I-C, Lee C-C, Tsai C-H, Tsai Y, Wan L, Hsu Y-A, et al. Association of GABRG2 polymorphisms with idiopathic generalized epilepsy. Pediatr Neurol. 2007;36:40\u20134.","journal-title":"Pediatr Neurol"},{"key":"3230_CR15","doi-asserted-by":"publisher","first-page":"157","DOI":"10.5114\/aoms.2016.63739","volume":"14","author":"AT Butil\u0103","year":"2018","unstructured":"Butil\u0103 AT, Zazgyva A, Sin AI, Szabo ER, Tilinca MC. GABRG2 C588T gene polymorphisms might be a predictive genetic marker of febrile seizures and generalized recurrent seizures: a case-control study in a Romanian pediatric population. Arch Med Sci. 2018;14:157\u201366.","journal-title":"Arch Med Sci"},{"key":"3230_CR16","doi-asserted-by":"publisher","first-page":"522","DOI":"10.1111\/epi.13670","volume":"58","author":"RS Fisher","year":"2017","unstructured":"Fisher RS, Cross JH, French JA, Higurashi N, Hirsch E, Jansen FE, et al. Operational classification of seizure types by the international league against epilepsy: position paper of the ILAE commission for classification and terminology. Epilepsia. 2017;58:522\u201330.","journal-title":"Epilepsia"},{"key":"3230_CR17","doi-asserted-by":"publisher","first-page":"512","DOI":"10.1111\/epi.13709","volume":"58","author":"IE Scheffer","year":"2017","unstructured":"Scheffer IE, Berkovic S, Capovilla G, Connolly MB, French J, Guilhoto L, et al. ILAE classification of the epilepsies: position paper of the ILAE commission for classification and terminology. Epilepsia. 2017;58:512\u201321.","journal-title":"Epilepsia"},{"key":"3230_CR18","unstructured":"Wyllie E, Gupta A, Lachhwani DK, editors. The treatment of epilepsy: principles & practice. Lippincott Williams & Wilkins; Philadelphia, USA. 2006."},{"key":"3230_CR19","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2009.02397.x","author":"P Kwan","year":"2010","unstructured":"Kwan P, Arzimanoglou A, Berg AT, Brodie MJ, Allen Hauser W, Mathern G, et al. Definition of drug resistant epilepsy: consensus proposal by the ad hoc Task Force of the ILAE Commission on therapeutic strategies. Epilepsia. 2010. https:\/\/doi.org\/10.1111\/j.1528-1167.2009.02397.x.","journal-title":"Epilepsia"},{"key":"3230_CR20","doi-asserted-by":"crossref","unstructured":"Serdar CC, Cihan M, Y\u00fccel D, Serdar MA. Sample size, power and effect size revisited: simplified and practical approaches in pre-clinical, clinical and laboratory studies. Biochemia medica. 2021 Feb 15;31(1):27-53","DOI":"10.11613\/BM.2021.010502"},{"key":"3230_CR21","doi-asserted-by":"publisher","first-page":"629","DOI":"10.1002\/1522-2683(200102)22:4<629::AID-ELPS629>3.0.CO;2-S","volume":"22","author":"C Heller","year":"2001","unstructured":"Heller C. Principles of DNA separation with capillary electrophoresis. Electrophoresis. 2001;22:629\u201343.","journal-title":"Electrophoresis"},{"key":"3230_CR22","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1046\/j.1528-1157.2001.042suppl.3008.x","volume":"42","author":"DM Treiman","year":"2001","unstructured":"Treiman DM. GABAergic mechanisms in epilepsy. Epilepsia. 2001;42:8\u201312.","journal-title":"Epilepsia"},{"key":"3230_CR23","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1016\/S1474-4422(19)30269-8","volume":"19","author":"CA Ellis","year":"2020","unstructured":"Ellis CA, Petrovski S, Berkovic SF. Epilepsy genetics: clinical impacts and biological insights. Lancet Neurol. 2020;19:93\u2013100.","journal-title":"Lancet Neurol"},{"key":"3230_CR24","doi-asserted-by":"crossref","unstructured":"The International League Against Epilepsy Consortium on Complex Epilepsies. Genome-wide mega-analysis identifies 16 loci and highlights diverse biological mechanisms in the common epilepsies. Nat Commun. 2018;9:5269. doi:10.1038\/s41467-018-07524-z","DOI":"10.1038\/s41467-018-07524-z"},{"key":"3230_CR25","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1016\/j.seizure.2018.06.004","volume":"60","author":"SS Abou El Ella","year":"2018","unstructured":"Abou El Ella SS, Tawfik MA, El Fotoh WMMA, Soliman OAM. The genetic variant \u201cC588T\u201d of GABARG2 is linked to childhood idiopathic generalized epilepsy and resistance to antiepileptic drugs. Seizure. 2018;60:39\u201343.","journal-title":"Seizure"},{"key":"3230_CR26","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1016\/j.seizure.2010.02.009","volume":"19","author":"R Kumari","year":"2010","unstructured":"Kumari R, Lakhan R, Kalita J, Misra U, Mittal B. Association of alpha subunit of GABAA receptor subtype gene polymorphisms with epilepsy susceptibility and drug resistance in north Indian population. Seizure. 2010;19:237\u201341.","journal-title":"Seizure"},{"key":"3230_CR27","doi-asserted-by":"publisher","first-page":"585","DOI":"10.4103\/0028-3886.105191","volume":"60","author":"LLG Gita\u00ed","year":"2012","unstructured":"Gita\u00ed LLG, de Almeida DH, Born JPL, Gameleira FT, de Andrade TG, Machado LC, et al. Lack of association between rs211037 of the GABRG2 gene and juvenile myoclonic epilepsy in Brazilian population. Neurol India. 2012;60:585\u20138.","journal-title":"Neurol India"},{"key":"3230_CR28","doi-asserted-by":"publisher","first-page":"1137","DOI":"10.1001\/archneur.59.7.1137","volume":"59","author":"C Kananura","year":"2002","unstructured":"Kananura C, Haug K, Sander T, Runge U, Gu W, Hallmann K, et al. A splice-site mutation in GABRG2 associated with childhood absence epilepsy and febrile convulsions. Arch Neurol. 2002;59:1137\u201341.","journal-title":"Arch Neurol"},{"key":"3230_CR29","doi-asserted-by":"publisher","first-page":"21079","DOI":"10.1038\/s41598-020-78333-y","volume":"10","author":"A El-Beshlawy","year":"2020","unstructured":"El-Beshlawy A, Salama AA, El-Masry MR, El Husseiny NM, Abdelhameed AM. A study of red blood cell alloimmunization and autoimmunization among 200 multitransfused Egyptian \u03b2 thalassemia patients. Sci Rep. 2020;10:21079.","journal-title":"Sci Rep"},{"key":"3230_CR30","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1016\/S0304-3940(03)00338-0","volume":"343","author":"J Nakayama","year":"2003","unstructured":"Nakayama J, Hamano K, Noguchi E, Horiuchi Y, Iwasaki N, Ohta M, et al. Failure to find causal mutations in the GABAA-receptor \u03b32 subunit (GABRG2) gene in Japanese febrile seizure patients. Neurosci Lett. 2003;343:117\u201320.","journal-title":"Neurosci Lett"},{"key":"3230_CR31","doi-asserted-by":"publisher","first-page":"547","DOI":"10.1002\/ana.23947","volume":"74","author":"J Kang","year":"2013","unstructured":"Kang J, Shen W, Macdonald RL. Trafficking-deficient mutant GABRG2 subunit amount may modify epilepsy phenotype. Ann Neurol. 2013;74:547\u201359.","journal-title":"Ann Neurol"},{"key":"3230_CR32","doi-asserted-by":"publisher","first-page":"1861","DOI":"10.1113\/jphysiol.2010.186999","volume":"588","author":"RL Macdonald","year":"2010","unstructured":"Macdonald RL, Kang J, Gallagher MJ. Mutations in GABAA receptor subunits associated with genetic epilepsies. J Physiol. 2010;588:1861\u20139.","journal-title":"J Physiol"},{"key":"3230_CR33","doi-asserted-by":"publisher","DOI":"10.1016\/j.yebeh.2019.07.031","volume":"121","author":"D P\u00e9rez-P\u00e9rez","year":"2021","unstructured":"P\u00e9rez-P\u00e9rez D, Fr\u00edas-Soria CL, Rocha L. Drug-resistant epilepsy: from multiple hypotheses to an integral explanation using preclinical resources. Epilepsy Behav. 2021;121:106430.","journal-title":"Epilepsy Behav"},{"key":"3230_CR34","doi-asserted-by":"publisher","first-page":"919","DOI":"10.1056\/NEJMra1004418","volume":"365","author":"P Kwan","year":"2011","unstructured":"Kwan P, Schachter SC, Brodie MJ. Drug-resistant epilepsy. N Engl J Med. 2011;365:919\u201326.","journal-title":"N Engl J Med"}],"container-title":["European Journal of Medical Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s40001-025-03230-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s40001-025-03230-x\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s40001-025-03230-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T08:06:31Z","timestamp":1761552391000},"score":1,"resource":{"primary":{"URL":"https:\/\/eurjmedres.biomedcentral.com\/articles\/10.1186\/s40001-025-03230-x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,27]]},"references-count":34,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["3230"],"URL":"https:\/\/doi.org\/10.1186\/s40001-025-03230-x","relation":{},"ISSN":["2047-783X"],"issn-type":[{"value":"2047-783X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,27]]},"assertion":[{"value":"15 June 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 September 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 October 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This study was approved by the institutional review board of the faculty of medicine, Mansoura University, Egypt. Informed consent was obtained from all individual participants included in the study.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"1020"}}