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5-羟色胺转运体基因启动子区CpG岛甲基化状态与精神分裂症Ⅰ型和Ⅱ型的关联
作者:张海生1 2  王伟1  余道军3  张顺泉2  谢健2 
单位:1. 浙江大学医学部临床心理室  浙江杭州310058 
2.
 杭州市第一人民医院临床心理科  浙江杭州310006 
3.
 杭州市第一人民医院检验科 
关键词:精神分裂症 甲基化 5-羟色胺转运体(5-HTT) 
分类号:R749.3
出版年,卷(期):页码:2011,19(3):289-292
摘要:

目的:探讨5-羟色胺转运体(5-HTT)基因启动子区CpG岛甲基化状态与精神分裂症Ⅰ型和Ⅱ型的关联。方法:运用特异性甲基检测PCR和直接测序法对62例精神分裂症Ⅰ型患者、38例Ⅱ型患者和50例健康被试5-HTT基因启动子区CpG岛甲基化状态进行检测。结果: 三组5-HTT基因启动子区CpG岛甲基化阳性率无显著性差异;精神分裂症Ⅰ型患者5-HTT基因启动子区CpG岛内位点甲基化率显著高于精神分裂症Ⅱ型患者和健康被试组。结论:5-HTT基因启动子区CpG岛内位点高甲基化可能是精神分裂症Ⅰ型的发病机制之一。

Objective:To explore the relationship between methylation status of CpG islands in the promoter region ofserotonin transporter gene(5-HTT) and type I or II schizophrenia.Methods:Methylation Specific PCR and DNA sequencing were used to detect the methylation status of CpG islands in 62 type I schizophrenia patients,38 type IIschizophrenia patients and 50 health subjects.Results:The methylation rates of CpG islands within the promoter region of5-HTT of the three groups are 52%(32/62),47%(18/38) and 50%(25/50),respectively.The methylation rates of loci inCpG islands within the promoter region of 5-HTT in type I schizophrenia group is significantly higher than those in type IIschizophrenia group and health subjects.Conclusion:The high methylation rate of loci in CpG islands within the promoter region of 5-HTT should be a possible factor to influence the nosogenesis of type I schizophrenia.

基金项目:
杭州市科技计划项目(20090833B06)
作者简介:
参考文献:

[1] Cardno AG,Gottesman II.Twin studies of schizophrenia:From bow-and-arrow concordances to star wars Mx andfunctional genomics.Am J Med Genet,2000,97:12-17;
[2] Abdolmaleky HM,Thiagalingam S,Wilcox M.Genetics andepigenetics in major psychiatric disorders:dilemmas,achievements,applications,and future scope.Am J Pharma-cogenomics,2005,5:149-160;
[3] Ohgane J,Yagi S,Shiota K.Epigenetics:the DNA methylationprofile of tissue-dependent and differentially methylatedregions in cells.Placenta,2008,29:29-35;
[4] Eastwood SL,Harrison PJ.Interstitial white matter neuronsexpress less reelin and are abnormally distributed in schizophrenia:Towards an integration of molecular and morphologicaspects of the neurodevelopmental hypothesis.MolPsychiatry,2003,8:821-831;
[5] Huang HS,Matevossian A,Whittle C,Kim SY,et al.Prefrontaldysfunction in schizophrenia involves mixed-lineageleukemia 1-regulated histone methylation at GABAergicgene promoters.J Neurosci,2007,27:11254-11262;
[6] Mill J,Tang T,Kaminsky Z,Khare T,Yazdanpanah S,et al.Epigenomic profiling reveals DNA-methylation changes associatedwith major psychosis.Am J Hum Genet,2008,82:696-711;
[7] Murphy BC,O'Reilly RL,Singh SM.Site-specific cytosinemethylation in S-COMT promoter in
[31] brain regions withimplications for studies involving schizophrenia.Am J MedGenet B Neuropsychiatr Genet,2005,133:37-42;
[8] Costello JF,Frühwald MC,Smiraglia DJ,et al.AberrantCpG-island methylation has non-random and tumour-typespecificpatterns.Nat Genet,2000,24:132-138.;
[9] Kundakovic M,Chen Y,Costa E,Grayson DR.DNA methyhransferase inhibitors coordinately induce expression ofthe human.Reelin and Ghtamic Acid Decarboxylase 67Genes-Mol Pharmacol,2007,71:644-653
[10] Iwamoto K,Bundo M,Yamada K,Takao H,et al.A familybasedand case-control association study of SOX
[10] inschizophrenia.Med Genet B Neurop Sychiatr Genet,2006,141:477-481
[11] Petronis A,Gottesman II,Kan P,Kennedy JL,et al.Monozygotictwins exhibit numerous epigenetic differences:Cluesto twin discordance.Schizophr Bull,2003,29:169-178
[12] Lesch KP.Variation of serotonergic gene expression:Neurodevelopmentand the complexity of response to psychopharmacologicdrugs.Eur Neuropsychopharmacol,2001,11:457-474
[13] Lesch KP,Mssner R.Genetically driven variation in serotoninuptake:Isthere a link to affective spectrum,neurodevelopmental,and neurodegenerativedisorders Biol Psychiatry,1998,44:179-192
[14] Jennings KA,Sheward WJ,Harmar AJ,Sharp T.Evidencethat genetic variation in 5-HT transporter expression islinked to changes in 5-HT2A receptor function.Neuropharmacology,2008,54:776-783
[15] Deltheil T,Guiard BP,Guilloux JP,Nicolas L,et al.Consequencesof changes in BDNF levels on serotonin neurotransmission,5-HTtransporter expression and function:Studiesin adult mice hippocampus.PharmacolBiochem Behav,2008,90:174-183
[16] Whalley HC,Baig BJ,Hall J,Job DE,et al.Effects of theBDNF val66met polymorphism on prefrontal brain functionin a population at high genetic risk of schizophrenia.Am JMed Genet B Neuropsychiatr Genet,2010,153:1474-1482
[17] Lo CH,Tsai GE,Liao CH,Wang MY,et al.Emotionalmanagement and 5-HT2A receptor gene variance in pa-tients with schizophrenia.Biol Psychol,2010,83:79-83
[18] Philibert R,Madan A,Andersen A,Cadoret R,et al.Serotonintransporter mRNA levels are associated with the methylationof an upstream CpG island.Am J Med Genet BNeuropsychiatr Genet,2007,144:101-105
[19] Kinnally EL,Capitanio JP,Leibel R,Deng L,et al.Epigeneticregulation of serotonin transporter expression and behaviorin infant rhesus macaques.Genes Brain Behav,2010,9:575-582
[20] Lesch KP.When the serotonin transporter gene meets adversity:The contribution of animal models to understandingepigenetic mechanisms in affective disorders and resilience.Curr Top Behav Neurosci,2011,7:251-280
[21] Allen NC,Bagade S,McQueen MB,Ioannidis JP,et al.Systematicmeta-analyses and field synopsis of genetic associationstudies in schizophrenia:the SzGene database.NatGenet,2008,40:827-834
[22] Kremen WS,Seidman LJ,Faraone SV,Toomey R,et al.Heterogeneity of schizoph-renia:A study of individualneuropsychological profiles.Schizophr Res,2004,71:307-321
[23] Crow TJ.Positive and negative schizophrenia symptoms andthe role of dopamine.Br J Psychiatry,1980,137:383-386
[24] 薛志敏,姚树桥.Ⅰ型与Ⅱ型精神分裂症患者的抽象和概括过程的比较研究.中国临床心理学杂志,1994,2:45
[25] 杨德森,姚芳传,陈彦芳.中国精神障碍分类与诊断标准CCMD-3.山东:山东科学技术出版社,2001.75
[26] 张明园.精神科评定量表手册.长沙:湖南科学技术出版社,1993.198-206
[27] 郑瞻培.精神分裂症的阴性症状.国外医学精神病学分册,1988,15:5-7
[28] Depoortère R,Bardin L,Auclair AL,Kleven MS,et al.F15063,a compound with D2/D3 antagonist,5-HT 1A agonistand D;
[4] partial agonist properties.II.Activity in modelsof positive symptoms of schizophrenia.Br J Pharmacol,2007,151:253-265
[29] Esterberg ML,Trotman HD,Holtzman C,Compton MT,etal.The impact of a family history of psychosis on age-atonsetand positive and negative symptoms of schizophrenia:A meta-analysis.Schizophr Res,2010,120:121-130
[30] Siegfried Z,Simon I.DNA methylation and gene expression.Wiley Interdiscip Rev Syst Biol Med,2010,2:362-371
[31] Anderson JE,Wible CG,McCarley RW,Jakab M,et al.AnMRI study of temporal lobe abnormalities and negative symptomsin chronic schizophrenia.Schizophr Res,2002,58:123-134
[32] 董燕,程宇琪,徐健,许秀峰,白燕.5-羟色胺转运体启动子区CpG岛甲基化与精神分裂症病因的相关研究.中国神经精神疾病杂志,2010,10:631-634

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