Ainara Barguilla, Pau Riera, Victoria Ros-Castelló, Elena Muino, Alba Sierra-Marcos
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引用次数: 0
Abstract
Background: Effectiveness and tolerability of anti-seizure medications (ASM) vary widely among individuals with epilepsy. Genetic polymorphisms may influence pharmacokinetic and pharmacodynamic responses, yet available evidence is heterogeneous and inconsistently translated into clinical practice.
Methods: A systematic search of eight databases (2000-2024) identified observational studies assessing associations between genetic variants and ASM response or adverse drug reactions. The review protocol was registered in PROSPERO (CRD420251237140). Two reviewers independently performed screening, data extraction and quality assessment using the Newcastle-Ottawa Scale. Owing to methodological heterogeneity, a narrative synthesis was conducted.
Results: A total of 168 studies were eligible. The strongest and most consistent associations involved HLA-B*15:02 and HLA-A*31:01 as predictors of severe cutaneous adverse reactions to carbamazepine, oxcarbazepine and phenytoin. CYP2C9 variants showed reproducible links to phenytoin toxicity. Associations involving ABCB1, SCN1A, SCN2A, GABRA1 and UGT2B7 for treatment response were reported, but findings varied across ASM classes and populations. Substantial ethnic variability was observed, particularly in Asian cohorts.
Conclusions: Only a limited number of genetic polymorphisms currently demonstrate sufficient consistency for clinical translation, mainly HLA alleles predicting severe cutaneous reactions and CYP2C9 variants associated with phenytoin toxicity. Larger multiethnic studies with standardized outcome definitions are needed to clarify the therapeutic role of additional markers and support broader pharmacogenomic implementation.
期刊介绍：
Expert Review of Neurotherapeutics (ISSN 1473-7175) provides expert reviews on the use of drugs and medicines in clinical neurology and neuropsychiatry. Coverage includes disease management, new medicines and drugs in neurology, therapeutic indications, diagnostics, medical treatment guidelines and neurological diseases such as stroke, epilepsy, Alzheimer''s and Parkinson''s.
Comprehensive coverage in each review is complemented by the unique Expert Review format and includes the following sections:
Expert Opinion - a personal view of the data presented in the article, a discussion on the developments that are likely to be important in the future, and the avenues of research likely to become exciting as further studies yield more detailed results
Article Highlights – an executive summary of the author’s most critical points
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