精神分裂症患者HTR2A基因多态性与帕利哌酮和利培酮临床疗效及安全性的关联研究  

Association study of the HTR2A polymorphisms with efficacy and safety of risperidone or paliperidone in Chinese schizophrenic patients

作　　者：杜波[1] 刘永桥[1] 刘飞虎[2] 肖卫东[3] 卢天兰[4] 李玲芝[4] 黄兰[4] 宓为峰[4] 张鸿燕[4] 

机构地区：[1]河北省第六人民医院药物临床试验机构办公室,河北保定071000 [2]西安市精神卫生中心医务科,西安710061 [3]武汉大学人民医院精神科,武汉430060 [4]北京大学精神卫生研究所,北京100191

出　　处：《中国临床药理学杂志》2011年第6期420-424,共5页The Chinese Journal of Clinical Pharmacology

摘　　要：目的观察中国汉族精神分裂症患者的5-羟色胺2A受体(HTR2A)基因多态性与帕利哌酮和利培酮治疗精神分裂症患者临床疗效与安全性的关联。方法入组201名精神分裂症患者,133例门诊或住院患者,随机接受12周帕利哌酮棕榈酸盐(50～150 mg/4周)或利培酮长效注射针剂(25～50 mg/4周)治疗,每2周进行1次疗效和安全性的评定;68例住院患者,接受4周利培酮片(2～6 mg·d-1)治疗,每周进行1次疗效和安全性评定;以试验结束时阳性阴性症状评定量表(PANSS)总减分率为主要疗效评价指标。共选择3个多态性位点,采用限制性酶切片段长度多态性或直接测序,获得基因型。结果 rs7997012各基因型可能与临床疗效相关联(P<0.05),位点rs6313和rs6311的各基因型间临床疗效的差别无统计学意义(P>0.05);位点rs6313和rs6311的各基因型与BARS、SAS评分变化及血AST、ALT升高的水平相关联(P<0.05)。结论 HTR2A基因与帕利哌酮及利培酮治疗的临床疗效和安全性可能有关联。Objective To study the relationship between gene polymorphisms of 5-hydroxytryptamine receptor 2A（HTR2A） genes and the clinical efficacy and safety in Han Chinese schizophrenic patients who were treated with risperidone or paliperidone.Methods Two hundreds and one schizophrenic patients were included in this study,one hundred and thirty thee inpatients or outpatients were randomized to take paliperidone palmitate（50-150 mg/4 week） or risperidone LAI（25-50 mg/2 week） for 12 weeks′ therapy,efficacy and safety examines were taken at every visit.Sixty eight inpatients or outpatients who were treated with risperidone tablets（2-6 mg·d-1） for 4 weeks were chosen.Efficacy and security examines was taken by every week.The main effect assessment was the final and baseline positive and negative syndrome scale（PANSS） total score reduced rate.The trial had chosen 3 SNPs,genotypes were detected by PCR-RFLP or direct sequencing.Results For clinical efficacy,it seemed that the genotypes of rs7997012 was associated with the clinical efficacy（P0.05）.There was no association between rs6313,rs6311 genotypes and clinical efficacy（P0.05）.As to the analysis between gene polymorphism and drug treatment safety,rs6313 and rs6311 genotypes might have influences on the BARS,SAS rating increase（P0.05）,and also rs6313 and rs6311 genotypes might be associated with the increasing level of AST and ALT（P0.05）.Conclusion The result give a possible association between HTR2A gene polymorphisms and the clinical efficacy or safety in Han Chinese schizophrenia patients treated with risperidone or paliperidone,which may be a guide for the individualized treatment of schizophrenia patients.

关 键 词：精神分裂症 HTR2A基因 多态性 帕利哌酮 利培酮 

分 类 号：R749.3[医药卫生—神经病学与精神病学] R971.41[医药卫生—临床医学]