多药耐药基因多态性与利培酮及其代谢物血药浓度的相关性
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篇名: 多药耐药基因多态性与利培酮及其代谢物血药浓度的相关性
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摘要: 目的:探讨我国汉族精神分裂症患者多药耐药基因(MDR1)多态性与利培酮、9-羟基利培酮及总活性物血药浓度的相关性。方法:选择2011年10月-2013年1月中南大学湘雅二医院精神卫生研究所的汉族精神分裂症住院患者78例,采用高效液相色谱-串联质谱法测定其利培酮、9-羟基利培酮和总活性物的血药浓度,采用聚合酶链-连接酶检测反应法检测患者MDR1 C1236T、G2677T和C3435T的基因分型,采用单因素方差分析考察MDR1基因多态性与利培酮、9-羟基利培酮及总活性物血药浓度/剂量校正比(C/D)值的相关性。结果:78例患者体内利培酮、9-羟基利培酮及总活性物的平均血药浓度分别为(13.58±8.31)、(25.62±15.52)、(39.24±25.76)ng/ml;C1236T、G2677T和C3435T各基因型分布频率均符合Hardy-Weinberg平衡(P>0.05);C1236T CT和TT型患者利培酮的C/D值高于CC型患者,G2677T TT型患者利培酮与总活性物的C/D值均高于GG型患者,差异均有统计学意义(P<0.05);而其他基因型患者体内各待测物C/D值间的差异均无统计学意义(P>0.05)。结论:汉族精神分裂症患者MDR1 C1236T和G2677T多态性与利培酮及总活性物的血药浓度相关。
ABSTRACT: OBJECTIVE: To discuss the correlation between multidrug resistance gene (MDR1) polymorphisms and plasma concentration of risperidone, 9-hydroxyrisperidone and total active substance in Han patients with schizophrenia. METHODS: 78 Han inpatients with schizophrenia in Mental Health Institute of Second Xiangya Hospital of Central South University from Dec. 2011 to Jan. 2013 were selected, LC-MS/MS was conducted to determine the plasma concentration of risperidone, 9-hydroxyrisperidone and total active substance, PCR-LDR was adopted to determine the genotyping of C1236T, G2677T and C3435T of patients, and one-way ANOVA was used to detect the correlation between C1236T, G2677T and C3435T polymorphisms and plasma concentration/dose calibration ratio (C/D) value of risperidone, 9-hydroxyrisperidone and total active substance. RESULTS: The average plasma concentrations of risperidone, 9-hydroxyrisperidone and total active substance for 78 patients were (13.58±8.31), (25.62±15.52) and (39.24±25.76) ng/ml, respectively; the distribution frequencies of C1236T, G2677T and C3435T met the Hardy-Weinberg equilibrium (P>0.05); the risperidone C/D value of patients with C12367T CT and TT genotype were higher than those with CC genotype, risperidone and total active substance C/D values of patients with G2677T TT genotype were higher than those with GG genotype, the differences were statistically significant (P<0.05); while there were no significant differences in analyte C/D values in other patients (P>0.05). CONCLUSIONS: The MDR1 C1236T and G2677T polymorphisms are associated with plasma concentration of risperidone and total active substance in Han patients with schizophrenia.
期刊: 2016年第27卷第26期
作者: 楼江,严伟,王刚,徐萍,李焕德,王飞
AUTHORS: LOU Jiang,YAN Wei,WANG Gang,XU Ping,LI Huande,WANG Fei
关键字: 多药耐药;基因多态性;利培酮;9-羟基利培酮;总活性物;血药浓度/剂量校正比;相关性
KEYWORDS: Multidrug resistance; Gene polymorphism; Risperidone; 9-hydroxyrisperidone; Total active substance; Plasma concentration/dose calibration ratio; Correlation
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