Assessment of clinically actionable pharmacogenetic markers to stratify anti-seizure medications.
Pharmacogenomics J
; 23(6): 149-160, 2023 Nov.
Article
em En
| MEDLINE
| ID: mdl-37626111
ABSTRACT
Epilepsy treatment is challenging due to heterogeneous syndromes, different seizure types and higher inter-individual variability. Identification of genetic variants predicting drug efficacy, tolerability and risk of adverse-effects for anti-seizure medications (ASMs) is essential. Here, we assessed the clinical actionability of known genetic variants, based on their functional and clinical significance and estimated their diagnostic predictability. We performed a systematic PubMed search to identify articles with pharmacogenomic (PGx) information for forty known ASMs. Functional annotation of the identified genetic variants was performed using different in silico tools, and their clinical significance was assessed using the American College of Medical Genetics (ACMG) guidelines for variant pathogenicity, level of evidence (LOE) from PharmGKB and the United States-Food and drug administration (US- FDA) drug labelling with PGx information. Diagnostic predictability of the replicated genetic variants was evaluated by calculating their accuracy. A total of 270 articles were retrieved with PGx evidence associated with 19 ASMs including 178 variants across 93 genes, classifying 26 genetic variants as benign/ likely benign, fourteen as drug response markers and three as risk factors for drug response. Only seventeen of these were replicated, with accuracy (up to 95%) in predicting PGx outcomes specific to six ASMs. Eight out of seventeen variants have FDA-approved PGx drug labelling for clinical implementation. Therefore, the remaining nine variants promise for potential clinical actionability and can be improvised with additional experimental evidence for clinical utility.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Farmacogenética
/
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos
Tipo de estudo:
Guideline
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Humans
País/Região como assunto:
America do norte
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article