Epilepsy research · 2017
Association of CYP2C9, CYP2A6, ACSM2A, and CPT1A gene polymorphisms with adverse effects of valproic acid in Chinese patients with epilepsy.
СтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Wang Can, Wang Ping, Yang Li-Ping, Pan Jing, Yang Xue, Ma Hong-Ying
Аннотация
OBJECTIVE: To explore the influence of CYP2C9, CYP2A6, ACSM2A, CPT1A gene polymorphisms on valproic acid (VPA) and its role in metabolism-related liver dysfunction in order to guide the clinical safety and rational use of VPA.
METHODS: One hundred two patients taking sodium valproate oral solution were genotyped. To assess the genotypes of relevant genes, the CYP2C9 gene was directly sequenced; for polymorphism classification, multiple Long-PCR electrophoresis was conducted for CYP2A6; and imLDR method was used for ACSM2A and CPT1A. GC-MS-SIM was used to determine the levels of VPA and 2-propyl-4-pentenoic acid (4-ene-VPA) in human plasma simultaneously.
RESULTS: CYP2C9 mutations had a significant impact on 4-ene-VPA concentration, in patients with wild-type CYP2C9 (CYP2C9*1), which has a greater capacity for VPA metabolism than the mutant type (CYP2C9*3), liver dysfunction was substantially higher. Patients with an ACSM2A polymorphism had higher levels of ALT and AST compared with wild-type (p<0.05), but the mutations had no effect on the VPA-related liver dysfunction (p>0.05). Among different CYP2A6 and CPT1A genotype groups, there was no significant correlation in the levels of VPA, 4-ene-VPA, ALT, AST or TB (p>0.05). The content of 4-ene-VPA had no direct correlation with the incidence of liver dysfunction.
CONCLUSIONS: Early detection of CYP2C9 gene polymorphisms may help to predict or prevent liver dysfunction caused by VPA. While the concentration of 4-ene-VPA was not suitable as an early warning index, the results provide clear theoretical guidance for the rational and safe clinical use of VPA.
METHODS: One hundred two patients taking sodium valproate oral solution were genotyped. To assess the genotypes of relevant genes, the CYP2C9 gene was directly sequenced; for polymorphism classification, multiple Long-PCR electrophoresis was conducted for CYP2A6; and imLDR method was used for ACSM2A and CPT1A. GC-MS-SIM was used to determine the levels of VPA and 2-propyl-4-pentenoic acid (4-ene-VPA) in human plasma simultaneously.
RESULTS: CYP2C9 mutations had a significant impact on 4-ene-VPA concentration, in patients with wild-type CYP2C9 (CYP2C9*1), which has a greater capacity for VPA metabolism than the mutant type (CYP2C9*3), liver dysfunction was substantially higher. Patients with an ACSM2A polymorphism had higher levels of ALT and AST compared with wild-type (p<0.05), but the mutations had no effect on the VPA-related liver dysfunction (p>0.05). Among different CYP2A6 and CPT1A genotype groups, there was no significant correlation in the levels of VPA, 4-ene-VPA, ALT, AST or TB (p>0.05). The content of 4-ene-VPA had no direct correlation with the incidence of liver dysfunction.
CONCLUSIONS: Early detection of CYP2C9 gene polymorphisms may help to predict or prevent liver dysfunction caused by VPA. While the concentration of 4-ene-VPA was not suitable as an early warning index, the results provide clear theoretical guidance for the rational and safe clinical use of VPA.