精神分裂症患者PTEN基因多态性与利培酮疗效及锥体外系症状的关联研究  

Association of phosphatase and tensin homolog gene polymorphisms with the efficacy and extrapyramidal symptoms of risperidone treatment in patients with schizophrenia

作　　者：高可润 禹顺英[2] 李华芳[2] GAO Kerun;YU Shunying;LI Huafang(Department of Psychiatry,Affiliated Mental Health Center,Zhejiang University School of Medicine(Hangzhou Seventh People's Hospital),Hangzhou,Zhejiang 310013,China;Shanghai Mental Health Center,Shanghai Jiao Tong University School of Medicine,Shanghai 200030,China)

机构地区：[1]浙江大学医学院附属精神卫生中心(杭州市第七人民医院)精神二科,浙江杭州310013 [2]上海交通大学医学院附属精神卫生中心,上海200030

出　　处：《预防医学》2024年第12期1060-1064,共5页China Preventive Medicine Journal

基　　金：浙江省医药卫生科技计划项目(2021RC025);杭州市医药卫生科技项目(A20200609)。

摘　　要：目的 探讨精神分裂症患者的磷酸酶与张力蛋白同源物(PTEN)基因多态性与利培酮治疗效果及锥体外系症状(EPS)的关联,为精神分裂症的药物基因组学研究和个体化治疗提供参考。方法 采用连续入组法纳入2019-2021年上海市精神卫生中心门诊或住院的急性发作期精神分裂症患者为研究对象。利培酮(4~8 mg/d)治疗8周,采用阳性和阴性症状量表(PANSS)评估病情,根据治疗前后PANSS减分率判断治疗有效性,采用辛普森-安格斯量表评估EPS。患者入组和治疗结束时采血提取DNA,采用SNaPshot法对PTEN基因的5个标签单核苷酸多态性(SNP)进行基因分型。采用多因素logistic回归模型分析不同基因型与利培酮治疗有效性及EPS的关联。结果 纳入精神分裂症患者144例,其中男性85例,占59.03%;女性59例,占40.97%。年龄M (QR)为30.50 (17.00)岁,病程M (QR)为5.50(9.00)年,使用利培酮剂量M (QR)为4.00 (0) mg/d。利培酮治疗有效60例,占41.96%;发生EPS 30例,占20.83%。多因素logistic回归分析结果显示,PTEN的5个SNP基因型均与利培酮治疗有效性无统计学关联(均P>0.05);rs17107001的GT+TT基因型与EPS发生风险降低有关(OR=0.110,95%CI:0.001~0.886)。结论 精神分裂症患者PTEN基因rs17107001的GT+TT基因型可能与利培酮治疗引起的EPS呈负相关。Objective To investigate the association between phosphatase and tensin homolog(PTEN)gene polymor⁃phisms with the efficacy of risperidone and extrapyramidal symptoms(EPS)in patients with schizophrenia,so as to pro⁃vide insights into pharmacogenomic studies and individualized treatment of schizophrenia.Methods The patients with schizophrenia in Shanghai Mental Health Center from 2019 to 2021 were selected using the consecutive enrollment meth⁃od.Risperidone(4-8 mg/d)was used to treat for 8 weeks.The symptoms were investigated using the Positive and Nega⁃tive Symptom Scale(PANSS),the treatment efficacy was evaluated using PANSS reducing rate before and after treat⁃ment,and EPS was evaluated using the Simpson-Angus Scale.Blood samples were drawn for DNA extraction at the time of patients enrollment and at the end of treatment.Five tag single nucleotide polymorphisms(SNPs)of PTEN gene were genotyped using the SNaPshot method.The association of PTEN genotypes with risperidone efficacy and EPS were using a multivariable logistic regression model.Results Totally 144 cases of patients with schizophrenia were enrolled,including 85 males(59.03%)and 59 females(40.97%).The median age was 30.50(interquartile range,17.00)years.The median course of disease was 5.50(interquartile range,9.00)years.The median dose of risperidone was 4.00(inter⁃quartile range,0)mg/d.There were 60 cases effectively treated with risperidone(41.96%),and 30 cases with EPS(20.83%).Multivariable logistic regression analysis showed that none of the five SNP genotypes of PTEN was statistical⁃ly associated with the efficacy of risperidone(all P>0.05),while the GT+TT genotype of rs17107001 was associated with a decreased risk of EPS(OR=0.110,95%CI:0.001-0.886).Conclusion The GT+TT genotype of the PTEN gene rs17107001 in patients with schizophrenia might be negatively associated with risperidone treatment-induced EPS.

关 键 词：精神分裂症 磷酸酶与张力蛋白同源物 单核苷酸多态性 利培酮 锥体外系症状 

分 类 号：R749.3[医药卫生—神经病学与精神病学]