DRD2(-141C Ins/Del)多态性与利培酮所致精神分裂症患者高泌乳素血症的相关性分析
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摘要
目的探讨垂体多巴胺2受体拮抗(DRD2)基因启动子区域-141C Ins/Del基因多态性与利培酮治疗导致的精神分裂症患者高泌乳素血症之间的相关性。方法按照美国精神病学会制定的精神障碍诊断与统计手册诊断标准,收集我院148例精神科汉族精神分裂症患者纳入研究组,另选取我院130例汉族体检健康者为对照组。两组均接受同一批次利培酮药物治疗,治疗前与治疗6周后抽取外周血,采用微粒酶免疫分析法对用药前后的泌乳素含量进行测定,采用聚合酶链式反应-限制性片段长度多肽分析(PCR-RELP)技术对外周血提取ERD2基因多态性位点(-141C Ins/Del)进行基因分型,利用吻合度检验检测Hardy-Weinberg平衡。结果 Hardy-weinberg遗传平衡吻合度检验显示,研究组与对照组各基因型分布符合与等位基因频率上差异均无统计学意义(P>0.05),符合遗传平衡差异;D2R2(-141C Ins/Del)基因多态性在性别、年龄、婚姻史、家族史、起病形式方面差异无统计学意义(P>0.05),在有无精神创伤史方面差异有统计学意义(P<0.05);研究组患者接受利培酮治疗6周后,血清泌乳素水平升高(P<0.05);Del携带者升高幅度显著低于Ins携带者,且Del/Del型泌乳素升高幅度最低(P<0.05)。结论 DRD2基因-141C Ins/Del多态性有望成为预测利培酮治疗精神分裂症患者所致高泌乳素血症的潜在生物学标志。
Objective To investigate the correlation between pituitary dopamine 2 receptor antagonist(DRD2)promoter region-141 C Ins/Del gene polymorphism with risperidone-induced hyperprolactinemia of schizophrenia patients.Methods Totally 148 Han patients with schizophrenia in our hospital were enrolled,and another 130 healthy Han control subjects were selected.The two groups were treated with risperidone of the same batch.The peripheral blood was taken before treatment and at 6 weeks after treatment,the content of prolactin before and after treatment was determined by microparticle enzyme immunoassay,and the polymerase chain reaction-restriction fragment length polypeptide analysis(PCR-RELP)was used to genotype ERD2 gene polymorphism loci(-141 C Ins/Del)extracted from peripheral blood,while Hardy-Weinberg balance was detected by equilibrium fit test.Results Hardy-weinberg genetic equilibrium fit test showed that there was no significant difference in genotypes distribution conforms or allele frequency between the two groups(P>0.05);D2 R2(-141 C Ins/Del)gene polymorphism had no significant difference between the different genders,age,marital history,family history or onset form(P>0.05),while it had significant difference between the different history of mental trauma(P<0.05);six weeks after risperidone treatment,the serum prolactin levels of study group were increased(P<0.05);the increase of Del carriers was significantly lower than that of Ins carriers,and the increase of Del/Del type prolactin was lowest(P<0.05).Conclusion DRD2 gene-141 C Ins/Del polymorphism is expected to be a potential biomarker for predicting risperidone-induced hyperprolactinemia in schizophrenia patients.
Objective To investigate the correlation between pituitary dopamine 2 receptor antagonist(DRD2)promoter region-141 C Ins/Del gene polymorphism with risperidone-induced hyperprolactinemia of schizophrenia patients.Methods Totally 148 Han patients with schizophrenia in our hospital were enrolled,and another 130 healthy Han control subjects were selected.The two groups were treated with risperidone of the same batch.The peripheral blood was taken before treatment and at 6 weeks after treatment,the content of prolactin before and after treatment was determined by microparticle enzyme immunoassay,and the polymerase chain reaction-restriction fragment length polypeptide analysis(PCR-RELP)was used to genotype ERD2 gene polymorphism loci(-141 C Ins/Del)extracted from peripheral blood,while Hardy-Weinberg balance was detected by equilibrium fit test.Results Hardy-weinberg genetic equilibrium fit test showed that there was no significant difference in genotypes distribution conforms or allele frequency between the two groups(P>0.05);D2 R2(-141 C Ins/Del)gene polymorphism had no significant difference between the different genders,age,marital history,family history or onset form(P>0.05),while it had significant difference between the different history of mental trauma(P<0.05);six weeks after risperidone treatment,the serum prolactin levels of study group were increased(P<0.05);the increase of Del carriers was significantly lower than that of Ins carriers,and the increase of Del/Del type prolactin was lowest(P<0.05).Conclusion DRD2 gene-141 C Ins/Del polymorphism is expected to be a potential biomarker for predicting risperidone-induced hyperprolactinemia in schizophrenia patients.
引文
[1] 石晶,王志仁,谭云龙,等.男性精神分裂症患者吸烟与多巴胺D2受体基因多态性的关联研究[J].中国心理卫生杂志,2017,31(11):833-839.
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[12] 秦秋红,姜涛.盐酸丁螺环酮片联合利培酮片对稳定期精神分裂症患者阴性症状的疗效观察[J].中国医药,2018,13(6):866-869.
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[14] Quintero J,Oyagüez I,González B,et al.Cost-minimisation analysis of paliperidone palmitate long-acting treatment versus risperidone long-acting treatment for schizophrenia in spain[J].Clin Drug Investig,2016,36(6):479-490.
[15] Gao X,Wang Y,Lang M,et al.Contribution of genetic polymorphisms and haplotypes in DRD2,BDNF,and opioid receptors to heroin dependence and endophenotypes among the Han Chinese[J].OMICS,2017,21(7):404-412.
[16] 韩勇,姜涛.氨磺必利与利培酮对精神分裂症患者血清泌乳素水平的影响[J].山东医药,2016,56(2):88-89.
[17] Matsusue A,Ishikawa T,Ikeda T,et al.DRD2/ANKK1 gene polymorphisms in forensic autopsies of methamphetamine intoxication fatalities[J].Leg Med,2018,33(1):6-9.
[18] 乔屹,梅轶,盛建华.多巴胺D2受体基因Taq1A多态性与利培酮、帕利哌酮所致高泌乳素血症的关系[J].临床精神医学杂志,2016,26(6):399-401.
[2] 谢筠,李美娟.多巴胺受体在精神分裂症认知受损中的作用研究进展[J].神经疾病与精神卫生,2017,17(9):669-671.
[3] 谭海英,李俊,秦绪英.语言沟通及心理护理在精神病患者中的应用探讨[J].世界最新医学信息文摘,2016,16(29):198-201.
[4] 张海枝,陈会慧,刘长鹰,等.卡利拉嗪:抗精神分裂症新药、多巴胺D3/D2受体部分激动剂[J].药物评价研究,2016,39(1):152-157.
[5] Frank GKW,Shott ME,DeGuzman MC,et al.Dopamine D2-141C Ins/Del and Taq1A polymorphisms,body mass index,and prediction error brain response[J].Transl Psychiatry,2018,8(1):102.
[6] 丛伟东,郑明坚,邹小芳,等.无抽搐电休克与重复经颅磁刺激治疗精神分裂症患者顽固性幻听的临床对照研究[J].齐齐哈尔医学院学报,2015,36(26):3903-3905.
[7] Sukasem C,Hongkaew Y,Ngamsamut N,et al.Impact of pharmacogenetic markers of CYP2D6 and DRD2 on prolactin response in risperidone-treated thai children and adolescents with autism spectrum disorders[J].J Clin Psychopharmacol,2016,36(2):141-146.
[8] 罗芮,冯湘玲,罗希,等.β-arrestin2基因多态性与湖南省汉族海洛因成瘾者美沙酮维持治疗反应的关联分析[J].中华流行病学杂志,2016,37(6):872-875.
[9] 王玮欣,程宇琪,许秀峰,等.精神分裂症患者非典型抗精神病药治疗前后的脑功能磁共振的研究进展[J].临床精神医学杂志,2016,26(4):278-279.
[10] Wang Y,Liu L,Xin L,et al.The-141C Ins/Del and Taq1A polymorphism in the dopamine D2 receptor gene may confer susceptibility to schizophrenia in Asian populations[J].J Clin Neurosci Neuroscience,2016,30(1):1-7.
[11] 王锦毓,杨庆国,汪心婷,等.DRD2-141C ins/del(rs 1799732)基因多态性与农村自杀未遂的关联性研究[J].伤害医学:电子版,2015,4(3):19-23.
[12] 秦秋红,姜涛.盐酸丁螺环酮片联合利培酮片对稳定期精神分裂症患者阴性症状的疗效观察[J].中国医药,2018,13(6):866-869.
[13] Wang S,Che T,Levit A,et al.Structure of the D2 dopamine receptor bound to the atypical antipsychotic drug risperidone[J].Nature,2018,555(7695):269-273.
[14] Quintero J,Oyagüez I,González B,et al.Cost-minimisation analysis of paliperidone palmitate long-acting treatment versus risperidone long-acting treatment for schizophrenia in spain[J].Clin Drug Investig,2016,36(6):479-490.
[15] Gao X,Wang Y,Lang M,et al.Contribution of genetic polymorphisms and haplotypes in DRD2,BDNF,and opioid receptors to heroin dependence and endophenotypes among the Han Chinese[J].OMICS,2017,21(7):404-412.
[16] 韩勇,姜涛.氨磺必利与利培酮对精神分裂症患者血清泌乳素水平的影响[J].山东医药,2016,56(2):88-89.
[17] Matsusue A,Ishikawa T,Ikeda T,et al.DRD2/ANKK1 gene polymorphisms in forensic autopsies of methamphetamine intoxication fatalities[J].Leg Med,2018,33(1):6-9.
[18] 乔屹,梅轶,盛建华.多巴胺D2受体基因Taq1A多态性与利培酮、帕利哌酮所致高泌乳素血症的关系[J].临床精神医学杂志,2016,26(6):399-401.