A real-life pilot study of the clinical application of pharmacogenomics testing on saliva in epilepsy. in Epilepsia open / Epilepsia Open. 2023 Sep;8(3):1142-1150. doi: 10.1002/epi4.12717. Epub 2023 May 15.
2023
ASL Vercelli
Tipo pubblicazione
Journal Article
Autori/Collaboratori (18)Vedi tutti...
Riva A
Department of Neurosciences Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), University of Genoa, Genoa, Italy.
Roberti R
Pediatric Neurology and Muscular Diseases Unit, IRCCS Istituto "Giannina Gaslini", Genoa, Italy.
D'Onofrio G
Science of Health Department, University Magna Grecia of Catanzaro, Catanzaro, Italy.
et alii...
Abstract
Response to antiseizure medications (ASMs) can be influenced by several gene polymorphisms, causing either lower efficacy or higher occurrence of adverse drug reactions (ADRs). We investigated the clinical utility of salivary pharmacogenomic testing on epilepsy patients. A commercialized pharmacogenomic salivary test was performed in a cohort of epileptic patients. Genetic variants on five genes (i.e., CYP1A2, CYP2C9, CYP2C19, EPHX1, and ABCB1) involved in common ASMs metabolism were selected. Twenty-one individuals (median age [Q(1) -Q(3) ]: 15 [6.5-28] years) were enrolled. Six patients harboring the homozygous *1F allele in CYP1A2 could have reduced chance of response to stiripentol due to fast metabolism. CYP2C9 had reduced activity in 10 patients (alleles *2 and *3), potentially affecting phenytoin (PHT), phenobarbital (PB), primidone, lacosamide (LCM), and valproic acid metabolism. Seven patients, carrying the *2 allele of CYP2C19, had an increased risk of ADRs with clobazam (CLB), PB, PHT, LCM, brivaracetam; while one individual with the *17 allele in heterozygosity reported a CLB fast metabolism. Six patients showed a CC polymorphism of EPHX1 associated with the impaired efficacy of carbamazepine. ABCB1 polymorphisms related to drug-resistance (3435 CC) or drug-sensitive phenotype (CT or TT) were found in 6 out of 7 patients. Pharmacogenomic testing on saliva proved easy and safe in clinical practice to convey information for the management of epileptic patients, especially those resistant to treatment or sensitive to severe ADRs.
Accesso banca dati bibliografica
Accedi alla scheda bibliografica del documento in PUBMED
PMID : 36840436
DOI : 10.1002/epi4.12717
Keywords
precision medicine; pharmacogenomics; epilepsy; antiseizure medications; Phenobarbital/therapeutic use; Saliva/metabolism; Cytochrome P-450 CYP2C9/genetics/metabolism; Pilot Projects; Cytochrome P-450 CYP2C19/genetics/metabolism/therapeutic use; Anticonvulsants/therapeutic use; Humans; Cytochrome P-450 CYP1A2; Pharmacogenetics; Clobazam/therapeutic use; Phenytoin/adverse effects; Epilepsy/drug therapy/genetics;