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癫痫患者CYP2C19基因多态性与丙戊酸钠血药浓度、疗效的相关性研究

Correlation between CYP2C19 gene polymorphism and the plasma concentration of sodium valproate and curative effect in patients with epilepsy.
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摘要 目的研究癫痫患者CYP2C19基因多态性与丙戊酸钠血药浓度、疗效的相关性。方法选取2022年8月至2023年7月乌鲁木齐市第四人民医院收治的115例癫痫患者作为研究对象,采用实时荧光聚合酶链反应(PCR)技术检测所有患者的CYP2C19基因型,同时给予丙戊酸钠治疗,将患者按CYP2C19基因型别分为强代谢型(*1/*1)47例、中间代谢型(*1/*2,*1/*3)50例和弱代谢型(*2/*2,*3/*3,*2/*3)18例,比较CYP2C19代谢型对血药浓度的影响;并根据丙戊酸钠治疗效果分为疗效良好组(n=85)和疗效不佳组(n=30),比较两组患者的一般资料,采用Logistic多因素回归分析影响丙戊酸钠治疗效果的因素。结果癫痫患者CYP2C19基因分型分布频率符合Hardy-Weinberg平衡定律检验;CYP2C19弱代谢型的丙戊酸钠血药浓度为(3.80±1.02)μg/mL,明显高于强代谢的(2.67±0.34)μg/mL和中间代谢型的(2.73±0.36)μg/mL,差异均有统计学意义(P<0.05),而强代谢型和中间代谢型的丙戊酸钠血药浓度比较差异无统计学意义(P>0.05);经单因素分析结果显示,月发病频率≥4次、继发性病因为热性惊厥、丙戊酸钠血药浓度<50μg/mL、服药依从性差、CYP2C19基因型为弱代谢型与丙戊酸钠治疗效果有关(P<0.05);经Logistic多因素回归分析结果显示,月发病频率≥4次、继发性病因为热性惊厥、丙戊酸钠血药浓度<50μg/mL、服药依从性差、CYP2C19基因型为弱代谢型均为影响丙戊酸钠治疗效果的独立危险因素(P<0.05)。结论癫痫患者的CYP2C19基因具有多态性,且与丙戊酸钠血药浓度及疗效具有相关性。因此,在采用丙戊酸钠治疗癫痫患者时,可检测CYP2C19基因分型,以指导癫痫患者的临床个体化治疗。 Objective To study the correlation between CYP2C19 gene polymorphism and the plasma concentration of sodium valproate and curative effect in patients with epilepsy.Methods A total of 115 patients with epilepsy admitted to Urumqi Fourth People's Hospital from August 2022 to July 2023 were selected as the research subjects.CYP2C19 genotypes in all patients were detected by real-time fluorescent polymerase chain reaction(PCR).The patients were treated with sodium valproate.According to CYP2C19 genotypes,the patients were divided into strong metabolism type(*1/*1;47 cases),moderate metabolism type(*1/*2,*1/*3;50 cases)and weak metabolism type(*2/*2,*3/*3,*2/*3;18 cases).The effects of different CYP2C19 metabolic types on plasma concentration were compared.According to curative effect of sodium valproate,the patients were divided into good effect group(n=85)and poor effect group(n=30),and general data of the two groups were compared.Multivariate logistic regression analysis was performed to identify the influencing factors of curative effect.Results The distribution frequencies of CYP2C19 genotypes in patients with epilepsy were in accordance with Hardy-Weinberg equilibrium test.The plasma concentration of sodium valproate in weak metabolism type[(3.80±1.02)μg/mL]was significantly higher than that in strong metabolism type[(2.67±0.34)μg/mL]and moderate metabolism[(2.73±0.36)μg/mL],P<0.05;there was no statistically significant difference between strong metabolism type and moderate metabolism type(P>0.05).Univariate analysis results showed that monthly onset frequency≥4 times,secondary diseases due to febrile convulsion,plasma concentration of sodium valproate<50μg/mL,poor medication compliance,and weak metabolism CYP2C19 genotype were related to the curative effect of sodium valproate(P<0.05).Multivariate logistic regression analysis results showed that monthly onset frequency≥4 times,secondary diseases due to febrile convulsion,plasma concentration of sodium valproate<50μg/mL,poor medication compliance,and weak metabolism CYP2C19 genotype were independent risk factors for the curative effect of sodium valproate(P<0.05).Conclusion CYP2C19 gene polymorphism in patients with epilepsy is correlated with the plasma concentration of sodium valproate and curative effect.Therefore,when sodium valproate is used to treat patients with epilepsy,CYP2C19 genotypes can be detected to guide clinical individualized treatment of patients with epilepsy.
作者 胡源 杨辉 虞梅 HU Yuan;YANG Hui;YU Mei(Department of Pharmacy,Medical Services Section,Urumqi 830000,Xinjiang,CHINA;Department of Pharmacy,Urumqi Fourth People's Hospital,Urumqi 830000,Xinjiang,CHINA)
出处 《海南医学》 CAS 2024年第4期476-480,共5页 Hainan Medical Journal
基金 新疆乌鲁木齐市卫生健康委科技计划项目(编号:202221)。
关键词 癫痫 CYP2C19基因多态性 丙戊酸钠血药浓度 疗效 影响因素 Epilepsy CYP2C19 gene polymorphism Plasma concentration of sodium valproate Curative effect Influencing factor
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