神经调节素1基因多态性位点rs35753503、rs3924999与利培酮治疗精神分裂症的关联

Association between Polymorphisms of rs3924999,rs35753505 in NRG1 Gene and the Efficacy of Risperidone in Patients with Schizophrenia

目的探讨神经调节素1(NRG1)基因多态性位点rs35753505、rs3924999与云南地区汉族精神分裂症利培酮治疗12周后临床疗效的关系.方法纳入122例精神分裂症住院患者,最终114例完成12周利培酮治疗、基因检测及相关量表评定,同时收集性别、年龄、受教育年限相匹配的187名汉族正常人群对照.采用微测序分型技术SNP检测基因多态性位点,采用Taq Man等位基因分型技术进行基因分型及基因频率分析,于治疗开始及治疗12周末进行阴性和阳性症状量表PANSS、个人和社会功能量表PSP、瑞文标准推理测验、韦氏智能测验数字识记法、数字划消测验测评,用两者的差值评估利培酮治疗精神分裂症的疗效.结果 (1)精神分裂症与对照的rs35753505、rs3924999两个基因多态性位点的基因型、等位基因频率分布差异无统计学意义;(2)rs35753505、rs3924999两个多态性位点不同基因型的基线临床资料比较未发现差异有统计学意义;(3)2个多态性位点不同基因型在利培酮治疗前后的数字划消一净分差值差异有统计学意义,其中rs35753505位点的2种基因型比较差异有统计学意义(P=0.010),即G/A组数字划消一净分差值较G/G组的差值高;rs3924999位点的3种不同基因型比较中,A/A与A/G比较差异有统计学意义(P=0.032),即A/A组数字划消一净分差值较A/G组的差值高;(4)利培酮治疗前后瑞文标准推理得分差值与rs35753505位点的2种基因型比较差异有统计学意义(P=0.004),即G/A组瑞文标准推理得分差值较G/G组的差值高;(5)利培酮治疗前后差值的相关分析及回归分析结果显示,数字划消二差值与基线的病程、基线的剂量、基线的瞬时记忆、基线数字划消二、三净分、rs35753505基因型有关.结论 rs35753505位点不同基因型患者经利培酮治疗后,注意的指向性和集中力、逻辑推理能力改善程度不同,G/A基因型患者的改善程度大于G/G基因型.

Objective To investigate the association between polymorphisms of rs35753505, rs3924999 in neuregulin-1（NRG1） gene and the efficacy of risperidone after 12 weeks treatment in Han patients with schizophrenia from Yunnan of China.Me thods A case-control study was conducted： 114 schizophrenic Han inpatients with 12 weeks single therapy of risperidone were randomly selected from July 2012 to March 2013 and 187 normal Han persons whose age and years of education matched the controls.Taq Man allelic genotyping technology was used to analyze NRG1 genotyping.Treatment effect of risperidone was evaluated by the positive and negative symptoms scale（PANSS）, PSP, Raven＇s Standard Progressive Matrices, Wechsler Intelligence Scale and Number Cancellation Test.Re s ults（1） There was no statistically difference in genotypes, allele frequencies of rs35753505, rs3924999 polymorphic locibetween schizophrenic inpatients and normal persons.（2） The baseline clinical data of patients with schizophrenia in different NRG1 gene polymorphism was not significant.（3） The value difference of Number Cancellation Test One between pre and post treatment of risperidone was related with different genotypes of two polymorphismsin NRG1 gene, there was statistically difference in two genotypes of rs35753505 loci： G/A group was higher than G/G group（P = 0.010） and in three genotypes of rs3924999 loci： A/A group was higher than A/G group（P = 0.032）.（4） The value difference of Reven＇s Standard Progressive Matrices between pre and post treatment of risperidone was related with rs35753505 polymorphic loci： G/A group was higher than G/G group（P = 0.004）（5） The result of correlation regression analysis between pre and post treatment of risperidone showed that the value difference of Number Cancellation Test Two was related with the baseline clinical data of course,dose,immediate memory, net score of Number Cancellation Test Two, Number Cancellation Test Three and the genotypes of rs35753505 loci.Conclus ion After 12 weeks treatment of risperidone： the improvement degree of patients＇ attention directivity and concentrated force in different genotypes of rs35753505 loci was different：G/A group was higher than G/G group.