Effect of CYP2C19 polymorphisms on serum valproic level acid in Chinese Han patients with schizophrenia
| Autor: | Chengkun Wang, Junxing Li, Mingfen Song, Xuan Ju, Jiyan Shi, Shuo-jia Wang, Pan Yan, Jiquan Liu |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Adult
Male Olanzapine China Genetics of the nervous system medicine.medical_specialty Genotype medicine.medical_treatment Science Single-nucleotide polymorphism CYP2C19 Real-Time Polymerase Chain Reaction Polymorphism Single Nucleotide Mass Spectrometry Article Young Adult Asian People Internal medicine Post-hoc analysis medicine Humans Allele Alleles Chromatography High Pressure Liquid Valproic Acid Multidisciplinary business.industry Middle Aged Cytochrome P-450 CYP2C19 Anticonvulsant Endocrinology Pharmacogenetics Schizophrenia Regression Analysis Diseases of the nervous system Medicine Anticonvulsants Female lipids (amino acids peptides and proteins) business medicine.drug |
| Zdroj: | Scientific Reports, Vol 11, Iss 1, Pp 1-6 (2021) Scientific Reports |
| ISSN: | 2045-2322 |
| Popis: | Valproic acid is an anticonvulsant, which is also widely used for treating psychiatric disorders. Some clinical trials have demonstrated benefits of valproic acid augmentation therapy in schizophrenia. Interindividual variability in valproic acid dose and serum concentration may reflect functional consequences of genetic polymorphisms in genes encoding drug-metabolizing enzymes. The aim of this study was to determine the relationship between serum concentrations of valproic acid and single nucleotide polymorphisms of the cytochrome P450 (CYP) 2C19 gene in patients with schizophrenia. All patients had been receiving fixed dose of valproic acid for at least 2 weeks. The daily doses were 0.5–1.5 g. No other drugs except olanzapine were coadministered. Serum concentrations of valproic acid were measured using the ultra-high performance liquid chromatography method with mass-spectrometric detection. The CYP2C19 (CYP2C19*2 G681A rs4244285 and CYP2C19*3 G636A rs4986893) genotypes were identified by real-time PCR analyses. The mean concentration/dose ratios of valproic acid were significantly higher in patients with CYP2C19 *1/*2 genotype (P CYP2C19 *2/*3 genotype (P CYP2C12 *1/*1 genotype. The mean concentration/dose ratios of valproic acid were significantly higher in patients with 1 (P P CYP2C19 than in those without mutated alleles. And the post hoc analysis revealed that the result has acceptable statistical (power (1 – β) = 0.8486 at type I level of 0.05) to support the observed significant associations for CYP2C19 SNPs and serum C/D ratios of valproic acid. The findings of this study suggest that the genetic polymorphisms of CYP2C19 significantly affect the steady-state serum concentrations of valproic acid in Chinese Han population. The determination of the CYP2C19 genotypes may be useful for dosing adjustment in schizophrenia patients on valproic acid therapy. |
| Databáze: | OpenAIRE |
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