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

林媛媛; 元静; 曾雷; 卫芋君; 张艳; 徐莉; 杨建中

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

昆明医科大学第二附属医院精神科

基金项目:

基金：国家自然科学基金资助项目 (81160170);

计量
- 文章访问数: 2370
- HTML全文浏览量: 879
- PDF下载量: 62
- 被引次数: 0
出版历程
- 收稿日期: 2018-02-11

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

Funds:

基金：国家自然科学基金资助项目 (81160170);

摘要

摘要: 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.
- 精神分裂症 /
- 神经调节素1 (NRG1) /
- 利培酮 /
- 关联研究
Abstract: 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.
- Schizophrenia /
- Neuregulin-1 (NRG1) /
- Risperidone /
- Association study

HTML全文

参考文献(28)

[1]	[1]KUROKI T, NAGAO N, NAKAHARA T.Neuropharmacology of second-generation antipsychotic drugs:a validity of the serotonin-dopamine hypothesis[J].Prog Brain Res, 2008, 172 (5) :199-212.
[2]蔡文婷, 谢莹, 肖剑文, 等.盐酸齐拉西酮片与利培酮治疗精神分裂症的疗效及安全性的对比分析[J].当代医学, 2017, 23 (04) :108-109.
[3]高良会, 王健, 孙秀丽, 等.比较氨磺必利与利培酮治疗精神分裂症的疗效与安全性[J].中国临床药理学杂志, 2013, 29 (09) :653-655.
[4]范小冬, 谢星星, 张杰, 等.齐拉西酮与利培酮治疗首发精神分裂症疗效与安全性的系统评价[J].川北医学院学报, 2017, 32 (02) :197-201.
[5]	[5]HARRISON P J, LAW A J.Neuregulin 1 and schizophrenia:genetics, gene expression, and neurobiology[J].Biol Psychiatry, 2006, 60 (2) :132-140.
[6]	[6]MEI L, NAVE K A.Neuregulin-ERBB signaling in the nervous system and neuropsychiatric diseases[J].Neuron, 2014, 83 (1) :27-49.
[7]	[7] MEI L, XIONG W C.Neuregulin 1 in neural development, synaptic plasticity and schizophrenia[J].Nat Rev Neurosci, 2008, 9 (6) :437-452.
[8]	[8]FALLS D L.Neuregulins:functions, forms, and signaling strategies[J].Exp Cell Res, 2003, 284 (1) :14-30.
[9]	[9]STEFANSSON H, SIGURDSSON E, STEINTHORSDOTTIR V, et al.neuregulin 1 and susceptibility to schizophrenia[J].Am J Hum Genet, 2002, 71 (4) :877-892.
[10]师乐, 李素霞, 邓佳慧, 等.《精神障碍诊断与统计手册》第5版中谱系障碍的变化[J].中国神经精神疾病杂志, 2015, 41 (04) :253-256.
[11]	[11]KAY S R, FISZBEIN A, OPLER L A.The Positive and Negative Syndrome Scale (PANSS) for Schizophrenia[J].Schizophrenia Bulletin, 1987, 13 (2) :261.
[12]侯晓君.小鼠前额叶皮层和丘脑网状核γ-氨基丁酸能神经环路的调控及其机制[D].杭州:浙江大学博士学位论文, 2014.
[13]	[13]STEFANSSON H, SARGINSON J, KONG A, et al.association of neuregulin 1 with schizophrenia confirmed in a scottish population[J].Am J Hum Genet, 2003, 72 (1) :83-87.
[14]	[14]AGIM Z S, ESENDAL M, BRIOLLAIS L, et al.Discovery, validation and characterization of Erbb4 and Nrg1haplotypes using data from three genome-wide association studies of schizophrenia[J].PLo S One, 2013, 8 (1) :e53042.
[15]	[15]LAW A J, WANG Y, SEI Y, et al.Neuregulin1-Erb B4-PI3K signaling in schizophrenia and phosphoinositide 3-kinase-p110delta inhibition as a potential therapeutic strategy[J].Proc Natl Acad Sci U S A, 2012, 109 (30) :12165-12170.
[16]	[16]PAPALEO F, YANG F, PATERSON C, et al.Behavioral, Neurophysiological, and Synaptic Impairment in a Transgenic Neuregulin1 (NRG1-IV) Murine Schizophrenia Model[J].J Neurosci, 2016, 36 (17) :4859-4875.
[17]唐君霞.DTNBP1和NRG1基因是中国汉族人群精神分裂症的易感基因[D].上海:中国科学院研究生院 (上海生命科学研究院) 博士学位论文, 2003.
[18]	[18]LI D, COLLIER D A, HE L.Meta-analysis shows strong positive association of the neuregulin 1 (NRG1) gene with schizophrenia[J].Hum Mol Genet, 2006, 15 (12) :1995-2002.
[19]	[19]KRUG A, MARKOV V, EGGERMANN T, et al.Genetic variation in the schizophrenia-risk gene neuregulin1 correlates with differences in frontal brain activation in a working memory task in healthy individuals[J].Neuroimage, 2008, 42 (4) :1569-1576.
[20]	[20]THIRUNAVUKKARASU P, VIJAYAKUMARI A A, JOHN J P, et al.An exploratory association study of the influence of dysbindin and neuregulin polymorphisms on brain morphometry in patients with schizophrenia and healthy subjects from South India[J].Asian Journal of Psychiatry, 2014, 10 (5) :62-68.
[21]	[21]MOSTAID M S, MANCUSO S G, LIU C, et al.Meta-analysis reveals associations between genetic variation in the 5'and 3'regions of Neuregulin-1 and schizophrenia[J].Transl Psychiatry, 2017, 7 (1) :e1004.
[22]	[22]LIN H F, LIU Y L, LIU C M, et al.Neuregulin 1 gene and variations in perceptual aberration of schizotypal personality in adolescents[J].Psychol Med, 2005, 35 (11) :1589-1598.
[23]	[23]HE B S, ZHANG L Y, PAN Y Q, et al.Association of the DISC1 and NRG1 genetic polymorphisms with schizophrenia in a Chinese population[J].Gene, 2016, 590 (2) :293-297.
[24]胡晓虹.精神分裂症与NRG1基因多态位点rs3924999的传递不平衡研究[D].汕头:汕头大学硕士学位论文, 2006.
[25]	[25]NAWAZ R, ASIF H, KHAN A, et al.Drugs targeting SNPrs35753505 of the NRG1 gene may prevent the association of neurological disorder schizophrenia in a Pakistani population[J].CNS Neurol Disord Drug Targets, 2014, 13 (9) :1604-1614.
[26]	[26]KANG C, YANG X, XU X, et al.Association study of neuregulin 1 gene polymorphisms with auditory P300 in schizophrenia[J].Am J Med Genet B Neuropsychiatr Genet, 2012, 159B (4) :422-428.
[27]	[27]SUMIYOSHI T.Possible dose-side effect relationship of antipsychotic drugs:relevance to cognitive function in schizophrenia[J].Expert Rev Clin Pharmacol, 2008, 1 (6) :791-802.
[28]	[28]YOON J S, KIM J M, LEE H, et al.Risperidone use in Korean patients with Alzheimer's disease:optimal dosage and effect on behavioural and psychological symptoms, cognitive function and activities of daily living[J].Hum Psychopharmacol, 2003, 18 (8) :627-633.

相关文章(20)

[1]	廉坤, 李咏梅, 施诚龙, 陈怡兰, 张磊, 杨薇, 许秀峰. 通过综合生物信息学方法探讨精神分裂症中关键线粒体自噬基因, 昆明医科大学学报.
[2]	尹文卅, 卢玉梅, 佟金莲, 聂胜洁, 阮冶. DNA甲基化与精神分裂症的研究进展, 昆明医科大学学报. doi: 10.12259/j.issn.2095-610X.S20230811
[3]	程甜甜, 尹文卅, 王佳, 卢玉梅, 陈炫羽, 聂胜洁, 刘林林. TMTC1基因多态性与精神分裂症的关联性, 昆明医科大学学报. doi: 10.12259/j.issn.2095-610X.S20231014
[4]	陈萌, 游顶云, 邢宸瑜, 章锦曼, 李洪英, 屈在卿, 朱蓓. 妊娠反应与孕期抑郁的关联研究, 昆明医科大学学报. doi: 10.12259/j.issn.2095-610X.S20221208
[5]	邹超杰, 唐义凯, 杜书文, 程宇琪. 调控海马神经元中CDC42蛋白活性对小鼠记忆和焦虑行为影响的研究, 昆明医科大学学报. doi: 10.12259/j.issn.2095-610X.S20221105
[6]	曾迪, 邵汉瑞, 邹英鹰, 阮永华. 孤儿受体GPR88在相关疾病中研究进展, 昆明医科大学学报. doi: 10.12259/j.issn.2095-610X.S20210723
[7]	冯梓乔, 张云桥, 游旭, 张闻宇, 龙青, 滕兆伟, 曾勇. IL-6在精神分裂症中的研究进展, 昆明医科大学学报.
[8]	高庆, 谢星, 罗莉. 利培酮、奥氮平、帕利哌酮对首发女性精神分裂症患者腰围和相关代谢指标的影响, 昆明医科大学学报.
[9]	吴杰, 张云桥, 滕兆伟, 游旭, 刘子君, 马语晗, 张闻宇, 冯梓乔, 龙青, 曾勇. 长链非编码RNA与精神分裂症相关性的研究进展, 昆明医科大学学报.
[10]	刘畅, 沈宗霖, 程宇琪, 许秀峰. 精神分裂症、双相情感障碍、抑郁症静息态功能磁共振研究的异同, 昆明医科大学学报.
[11]	姜红燕, 冉柳毅, 吴桂霞, 许秀峰, 于黎. NDST3基因多态性与云南汉族精神分裂症的关联, 昆明医科大学学报.
[12]	雷杰鹏, 杨丽, 罗诚, 张体苑, 吕鑫, 李胜巧, 林海波. 帕利哌酮与利培酮在治疗首发儿童青少年精神分裂症的临床对照, 昆明医科大学学报.
[13]	冯国华, 卫芋君, 元静, 张艳, 曾雷, 杨建中. DRD2和DRD3基因多态性与利培酮治疗精神分裂症疗效的关联性, 昆明医科大学学报.
[14]	朱俊艳. 内观疗法对精神分裂症伴发抑郁的影响, 昆明医科大学学报.
[15]	侯羲. 精神分裂症患者入院时生命质量相关因素, 昆明医科大学学报.
[16]	敖磊. 糖尿病对精神分裂症患者认知功能的影响, 昆明医科大学学报.
[17]	侯羲. 不同病程组精神分裂症患者住院治疗成本-效果分析, 昆明医科大学学报.
[18]	胡东辉. 阿立哌唑与利培酮治疗阿尔茨海默病性痴呆精神症状的临床对照, 昆明医科大学学报.
[19]	刘玲. UGT1A1基因多态性与昆明地区重症新生儿黄疸的遗传关联性研究, 昆明医科大学学报.
[20]	蒋榆辉. 云南省迁延性新生儿黄疸与UGT 1A1基因多态性的遗传关联性研究, 昆明医科大学学报.