精神分裂症患者多药耐药基因多态性与帕利哌酮和注射用利培酮微球临床疗效的关联研究  

Association of multidrug resistance 1 gene polymorphism with the clinical efficacy of paliperidone and risperidone in schizophrenic patients

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

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

出　　处：《中华精神科杂志》2010年第3期167-171,共5页Chinese Journal of Psychiatry

基　　金：卫生部临床学科重点项目资助项目（51）

摘　　要：目的 探讨中国汉族精神分裂症患者多药耐药基因（multidrug resistance gene 1,MDR1）多态性与帕利哌酮和注射用利培酮微球治疗精神分裂症的临床疗效的关联.方法 对入组的133例精神分裂症患者分别给予帕利哌酮或注射用利培酮微球治疗12周;以阳性与阴性症状量表（PANSS）作为主要疗效评价工具,以治疗结束时临床总体印象-严重程度量表（CGI-S）及人际和社交能力量表（PSP）作为次要疗效评价工具;每2周进行PANSS评定;应用聚合酶链反应-限制性片段长度多态性和DNA测序的方法检测受试者多药耐药基因5个多态性位点的基因型,应用卡方检验和方差分析法分析各基因型与临床疗效的关联性.结果 MDR1基因多态性与主要疗效指标PANSS减分率及有效率的关联分析中未发现差异有统计学意义（P＞0.05）;非参数检验分析显示：位点rs1045642 CC基因型携带者在阴性症状条目抽象思维障碍（Z=-2.62,P=0.009）及阳性症状条目夸大（Z=-2.84,P=0.005）有较好疗效;rs2032582位点GG基因型携带者在一般病理学症状条目紧张改善较差（Z=-2.50,P=0.012）;rs1202169位点A等位基因携带者在一般病理学条目主动社会回避改善较好（Z=-2.09,P=0.036）;rs13233308位点CC基因型携带者在一般病理学条目罪恶观念（Z=-2.09,P=0.036）和交流缺乏自发性和主动性疗效（Z=-2.73,P=0.006）改善不佳,该位点携带TT基因型的个体在紧张条目的 疗效改善较好（Z=-2.54,P=0.011）.次要疗效指标分析显示,rs1045642位点C等位基因与PSP评分高度相关（Z=-2.18,P=0.029）.结论 多药耐药基因多态性可能并不影响中国汉族精神分裂症患者帕利哌酮和注射用利培酮微球的临床疗效,但与妄想、社交回避的改善可能相关.Objective To explore the association between multidrug resistance 1gene （MDR1）polymorphisms with the therapeutic efficacy of paliperidone （9-hydroxyrisperidone） and risperidone in Han Chinese schizophrenic patients. Methods One hundred and thirty-three schizophrenic patients were given paliperidone or risperidone LAI for a 12-week treatment. The PANSS was used to assess the main therapeutic efficacy, and the Clinical Global Impression-Severity （CGI-S） scale and the Personal and Social Function scale （PSP） were used to as the secondary therapeutic efficacy assessments. The patients were evaluated every 2 weeks. The polymerase chain reaction-based-restriction fragment length polymorphisms （PCRRFLP） and DNA sequencing were used to detect the genotypes of 5 candidate single nucleotide polymorphisms （SNPs）. The association between MDR1 genotypes with the therapeutic efficacy was analyzed using the chi-square and ANOVA tests. Results There were no statistical significant differences between MDR1 gene polymorphism and the PANSS reduction rate or clinical efficacy rate（P 〉0.05）. Non-parameter tests revealed that, patients carrying CC genotype of locus rs1045642 had better efficacy in negative symptom item ＇ difficulty in abstract thinking＇ （ Z = - 2. 62, P = 0. 009 ） and positive symptom item ＇ grandiosity ＇（Z = -2. 84,P =0. 005）, and GG genotype of locus rs2032582 carriers had worse improvements in general psychopathology item ＇tension＇ （Z = -2.50,P =0. 012）, and as to patient who carried A allele of locus rs1202169 had better improvements in general psychopathology item ＇active societal avoidance＇（Z = -2. 09,P =0. 036）, and CC genotype of locus rs13233308 carriers had worse improvements in items ＇ guilt feelings＇ （Z = - 2. 09, P = 0. 036） and ＇ lack of spontaneity and flow of conversation＇ （Z = - 2.73,P = 0. 006） ,TT genotype carriers had a better improvement in item ＇ tension＇ （ Z = - 2. 54, P = 0. 011）.Secondary clinical efficacy an

关 键 词：精神分裂症 多药耐药基因 MDR 多态性 限制性片段长度 利哌立酮 帕利哌酮 

分 类 号：R749.3[医药卫生—神经病学与精神病学]