多巴胺D4受体第3外显子48 bp可变重复序列多态性与抽动障碍的传递不平衡检测

目的研究多巴胺D4受体第3外显子48 bp可变重复序列(DRD4 exonⅢ48bpVNTR)多态性是否与抽动障碍(tic disorder, Tic)存在关联.方法采用国际标准化的<Tourette综合征及其相关疾病遗传研究定式检查提纲>收集病史,运用核心家系传递不平衡分析方法(transmission disequilibrium test, TDT)对122个核心家系进行关联分析,根据是否合并注意缺陷多动障碍(attention deficit and hyperactivity disorder, ADHD),将122个核心家系分为合并ADHD的抽动障碍组[合并ADHD的Tourette综合征(Tourette syndrome, TS)和慢性抽动障碍(chronic tic, CT),共40例,TS&ADHD]和抽动障碍组[TS和CT,共82例,TS&CT]两组,采用聚合酶链反应、可变重复序列多态性分析等技术,进行抽动障碍与DRD4 exonⅢ48 bpVNTR多态性的TDT分析.结果在这一多态性位点存在5个等位基因,分别为DRD4 exonⅢ48 bp的2～6个重复等位基因.总体上没有发现抽动障碍与DRD4 exonⅢ48 bpVNTR多态性存在传递不平衡(χ2＝7.44,P＝0.12),进一步对不伴ADHD的抽动障碍组进行的TDT分析也没有发现存在这一位点的传递不平衡(χ2＝3.38,P＝0.50);而在合并ADHD的抽动障碍组中发现,合并ADHD的抽动障碍与DRD4 exonⅢ48 bpVNTR多态性在总体上存在传递不平衡(χ2＝11.74,P＝0.02),进一步对单个等位基因的TDT分析显示,合并ADHD的抽动障碍与DRD4 exonⅢ48 bp的5个重复和6个重复等位基因(长重复等位基因)存在传递不平衡(χ2＝10.57,P＝0.032,χ2＝6.13,P＝0.01).结论 DRD4 exonⅢ48 bpVNTR长重复等位基因与合并ADHD的抽动障碍存在关联,DRD4 exonⅢ48 bpVNTR长重复等位基因可能是中国人群合并ADHD的抽动障碍的遗传危险因素.     

血浆载脂蛋白B基因3''端可变数目串联重复序列的结构研究

目的研究载脂蛋白B（apollpoprotein B，apoB）基因apoB 3’端可变数目串联重复序列（variable number of tandem repeats，VNTR）多态性与序列结构。方法应用聚合酶链反应结合琼脂糖凝胶电泳技术检测了522名随机抽取的体检人员apoB基因3’VNTR多态性，选取26个样本的PCR产物进行DNA序列测定。结果分离出16个等位基因即高变单元（hypervariable element，HVE），其中杂合子多于纯合子，最大的等位基因是HVE58，最小的是HVE24；HVE34频率最高40．4％，其次是HVE32，占34．7％。对26名60个等位基因进行的DNA核苷酸测序中，发现一个等位基因异构体（Y-A=ATAATTAAATATTT），4个结构模式。结论中国人与欧美人群在apoB基因3’VNTR等位基因频率分布上存在明显差异，在等位基因异构体与结构模式上也存在不同。     

血浆载脂蛋白B基因3′端可变数目串联重复序列的结构研究

目的研究载脂蛋白B(apolipoproteinB,apoB)基因apoB3′端可变数目串联重复序列(variable numberoftandemrepeats,VNTR)多态性与序列结构。方法应用聚合酶链反应结合琼脂糖凝胶电泳技术检测了522名随机抽取的体检人员apoB基因3′VNTR多态性,选取26个样本的PCR产物进行DNA序列测定。结果分离出16个等位基因即高变单元(hypervariableelement,HVE),其中杂合子多于纯合子,最大的等位基因是HVE58,最小的是HVE24;HVE34频率最高40.4%,其次是HVE32,占34.7%。对26名60个等位基因进行的DNA核苷酸测序中,发现一个等位基因异构体(Y A=ATAATTAAATATTT),4个结构模式。结论中国人与欧美人群在apoB基因3′VNTR等位基因频率分布上存在明显差异,在等位基因异构体与结构模式上也存在不同。     

多巴胺D3受体基因Ser-9-Gly多态性精神分裂症的关联研究

为探讨精神分裂症与多巴胺 D3受体基因 ( dopamine D3receptor gene,DRD3) Ser-9-Gly多态性是否关联。应用PCR-RFLP方法检测了广州地区汉族人群中 1 2 3例家族史阴性、1 1 3例家族史阳性精神分裂症患者、1 6 8例家族史阴性患者父母和 4 7例正常老年人中多巴胺 D3受体基因 Ser-9-Gly多态性 ,并对多巴胺 D3受体基因各等位基因及基因型与精神分裂症进行了相关分析 ,DRD3与精神分裂症、患者性别及家族史均无关联 ( P>0 .0 5 )。提示广州地区汉族人群中DRD3基因 Ser-9-Gly多态性与精神分裂症没有关联。     

抽动秽语综合征汉族患者的执行功能及与多巴胺D4受体第3外显子48bp可重复序列多态性

目的:了解多巴胺D4受体基因第3外显子48bp可重复序列多态性(DRD4 exonIII NTR)与抽动秽语综合征(Gillesdela Tourette syndrome,GTS)患者执行功能缺陷之间的关系。方法:对86例GTS患者进行威斯康星卡片测验(Modified Wisconsin Card sortingtest,WCST)、Stroop色词测验(Strooptest)和连线测验,并和51例正常对照组进行比较;利用PCR技术对GTS患者进行了DRD4exonIII48bpVNTR分析。结果:与正常对照组比较,GTS组在Stroop测验中的C错误数[(44.39±65.3)vs.(20.50±10.85),P0.01]等(包括C纠错数、C时间、CW正确数、CW错误数、CW纠错数和CW时间)、连线测验A时间[(69.80±25.84)vs.(35.69±8.25),P0.01](包括连线B时间、错误数、犯规数)、WCST正确数[(44.39±65.37)vs.(27.49±10.85),P0.01](错误数、持续错误数、非持续错误数和分类数)等测验项目上成绩较差,从共病情况来看,注意缺陷多动综合征共病组在Stroop测验部分项目上比单纯GTS组要差;从GTS组内分析来看,DRD4exonIII48bpVNTR和各神经心理学测验成绩没有关联。结论:抽动秽语综合征患者存在执行功能缺陷,DRD4exonIII48bpVNTR和抽动秽语综合征执行功能缺陷之间可能没有关联。     

多巴胺D2受体基因启动子多态性与帕金森病的关联研究

目的 探讨中国汉族人群多巴胺D2受体基因启动子多态性在帕金森病（Parkinson's disease,PD)遗传易感性中的作用。方法 采用病例－对照关联分析，聚合酶链反应－限制性片段长度多态性方法分析了123例PD患者（PD组）与124名健康成人（对照组）多巴胺D2受体基因启动子多态性。结果 PD组－141△C等位基因频率为8．5％，对照组为11．7％；两组差异无显著性（P＞0．05）；中国汉族人PD组组和对照组－141△C等位基因频率明显高于意大利南部人群，差异有显著性（P＜0．05）。结论中国汉族人群多巴胺D2受体基因启动子多态性与PD的遗传易感性无关，该多态性有明显的种族差异。     

DRD4第3外显子48 bp可变重复序列多态性与幼儿气质的相关研究

目的　探讨多巴胺 D4受体第 3外显子 48bp可变重复序列多态性 (dopamine D4receptorexon 48bp variant number tandem repeat,DRD4exon 48bp VNTR)与幼儿气质的关系。方法　采用聚合酶链反应和 VNTR多态性分析技术 ,检测了成都地区 2 34名汉族幼儿的 DRD4基因多态性 ;用 1～3岁幼儿气质量表测查其气质 ;根据 DRD4外显子 48bp VNTR等位基因重复片段大小分为 S组 (基因型中只含等位基因 2 )和 L 组 (基因型中至少含有一个等位基因 3或 5、9) ,对各组幼儿气质类型和气质纬度进行相关分析 ,统计方法采用 χ2检验和 t检验。结果　不同基因型幼儿其气质类型没有差异 (χ2 =0 .795 9,ν=3,P>0 .0 5 ) ;DRD4外显子 48bp VNTR长重复基因 (L)组幼儿气质纬度中的注意力分散度得分较低 (t=2 .95 5 ,P=0 .0 0 3)。结论　 DRD4外显子 48bp VNTR长重复等位基因与注意力分散度有关     

相同多态性位点对结核分枝杆菌北京家族菌株多位点可变数目串联重复序列基因型构成的影响

目的 探讨多态性相同的位点对北京家族结核分枝杆菌多位点可变数目串联重复序列(MIRU-VNTR)基因分型的影响,为合理选择分型位点提供科学依据.方法 分别选取9个及12个位点,构成4组MIRU-VNTR位点组合,其中,9位点组成的两个组合中,分别有两个不同位点(MIRU40/MIRU16)多态性一致,其余为相同位点;12位点的两个组合则分别包括另外两个多态性相同的位点(MIRU39/MIRU31).进行聚类分析,比较含有相同多态性的不同位点组合的分辨能力、成簇能力以及基因型特点.结果 9位点两个组合都将菌株分为三群,其中,Ⅲ群菌株仅有1株相同,分别占组合1、2的2.0％和1.6％.12位点组合也将菌株分为三群,第Ⅱ群菌株组成差异非常明显,完全没有相同的菌株.结论 多态性相同的位点对北京家族菌株MIRU-VNTR基因分型影响较大.在选择MIRU-VNTR分型位点时,应不仅仅检验位点的分辨能力和对成簇的影响,还应考虑有相同/相近多态性的位点对基因型构成的影响.     

多巴胺突触前膜转运载体基因多态性与帕金森病

目的 研究多巴胺突触前膜转运载体（dopamine transporter,DAT)的基因多态性与帕金森病（Parkinson's disease,PD)的关系。方法 比较了85名健康对照和128例PD患者（包含发病年龄小于或等于50岁的早发型PD亚组和发病年龄大于50岁的晚发型PD亚组）的DAT基因串联重复可变数（variable number of tandem repeat,VNTR)多态性分布。结果 该多态性位点的基因型和等位基因分布,在对照组和PD患者之间差异有显著性;晚发型PD与7拷贝等位基因强相关,与11拷贝等位基因弱相关,早发型PD主要与9拷贝等位基因相关。结论 该结果不仅支持DAT与PD相关的假说,而且提示了DAT基因VNTR多态性与PD发病年龄的可能关系。     

Lack of association between dopamine receptor D4 variable numbers of tandem repeats gene polymorphism and smoking

Nicotine addiction, related to cigarette smoking, develops as a product of the complex interactions between social, environmental and genetic factors. Genes encoding the components of the dopaminergic system are thought to be associated with smoking. Literature data showed not only an association, but also a lack of association between variable number of tandem repeats (VNTR) polymorphism located in the third exon of dopamine D4 receptor (DRD4) gene and smoking. Repetitive sequence of DRD4 VNTR is 48 bp long and maximum 11 tandem copies were reported in humans. Presence of alleles with 6 and more repeats (i.e. long alleles) was associated with greater tendency to novelty seeking and addictive behaviors than the presence of 5 and less alleles (short alleles). The aim of this study was to determine the association between VNTR in DRD4 gene and present smoking status in ethnically homogenous Caucasian population from the Eastern European (Croatian) origin. Genotyping was done in 565 healthy subjects, 511 men and 54 women, respectively, who were subdivided into 176 smokers and 389 nonsmokers. Logistic regression analyses, adjusted for age and sex, revealed the lack of significant (p > 0.05) effect of the 4/4, 4/7 and 7/7 genotypes, or carriers of the long and short allele, or all genotypes of the DRD4 VNTR on smoking status. The results of this study failed to confirm the hypothesis that long allele of the DRD4 VNTR is associated with smoking status in Caucasian subjects.     

D2 and D4 dopamine receptor polymorphisms and personality

The relationship of various dimensions of temperament, measured by the Tridimensional Personality Questionnaire (TPQ), to polymorphisms of the D₂ dopamine receptor (DRD2) and D₄ dopamine receptor (DRD4) genes was determined in 119 healthy Caucasian boys who had not yet begun to consume alcohol and other drugs of abuse. Total Novelty Seeking score of the TPQ was significantly higher in boys having, in common, all three minor (A1,B1, and Intron 6 1) alleles of the DRD2 compared to boys without any of these alleles. Boys with the DRD4 7 repeat (7R) allele also had a significantly higher Novelty Seeking score than those without this allele. However, the greatest difference in Novelty Seeking score was found when boys having all three minor DRD2 alleles and the DRD4 7R allele were contrasted to those without any of these alleles. Neither the DRD2 nor the DRD4 polymorphisms differentiated total Harm Avoidance score. Whereas subjects having all three minor DRD2 alleles had a significantly higher Reward Dependence 2 (Persistence) score than subjects without any of these alleles, no significant difference in this personality score was found between subjects with and without the DRD4 7R allele. In conclusion, DRD2 and DRD4 polymorphisms individually associate with Novelty Seeking behavior. However, the combined DRD2 and DRD4 polymorphisms contribute more markedly to this behavior than when these two gene polymorphisms are individually considered. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 81:257–267, 1998. © 1998 Wiley-Liss, Inc.     

山西地区汉族人群六个短串联重复序列基因座的遗传多态性

目的 分析山西地区汉族D9S925、D11S2368、D14S608、D15S659、D17S1290、D20S470等6个短串联重复序列(short tandem repeat,STR)基因座的遗传多态性.方法 根据GenBank资料合成D9S925、D11S2368、D14S608、D17S1290、D20S470基因座引物,自行设计D15S659引物,对山西汉族194个无关个体DNA进行PCR扩增,3130型基因分析仪电泳分析,GeneMapper(R)3.2分析等位基因片段大小,测序后命名.结果 6个STR基因座基因型频率分布符合Hardy-Weinberg平衡(P＞0.05).6个STR基因座的多态性信息含量在0.750～0.860之间,杂合度在0.756～0.894之间,个体识别力在0.920～0.965之间,非父排除概率在0.519～0.784之间,累积非父排除率为0.9988,累积个体识别能力为0.99999998.结论 本次研究的6个STR基因座在山西汉族群体中等位基因频率分布均匀,多态性好,适用于法医学亲子鉴定及个人识别,可作为现有基因座的补充.     

山西地区汉族人群六个短串联重复序列基因座的遗传多态性

目的 分析山西地区汉族D9S925、D11S2368、D14S608、D15S659、D17S1290、D20S470等6个短串联重复序列(short tandem repeat,STR)基因座的遗传多态性.方法 根据GenBank资料合成D9S925、D11S2368、D14S608、D17S1290、D20S470基因座引物,自行设计D15S659引物,对山西汉族194个无关个体DNA进行PCR扩增,3130型基因分析仪电泳分析,GeneMapper(R)3.2分析等位基因片段大小,测序后命名.结果 6个STR基因座基因型频率分布符合Hardy-Weinberg平衡(P＞0.05).6个STR基因座的多态性信息含量在0.750～0.860之间,杂合度在0.756～0.894之间,个体识别力在0.920～0.965之间,非父排除概率在0.519～0.784之间,累积非父排除率为0.9988,累积个体识别能力为0.99999998.结论 本次研究的6个STR基因座在山西汉族群体中等位基因频率分布均匀,多态性好,适用于法医学亲子鉴定及个人识别,可作为现有基因座的补充.     

Association study between the dopamine D4 receptor gene and schizophrenia

The dopamine D4 receptor is of major interest in schizophrenia research due to its high affinity for the atypical neuroleptic cloza-pine and a high degree of variability in the receptor gene (DRD4). Although several genetic linkage analyses performed on schizophrenia multiplex families from different regions of the world have either excluded or failed to prove that DRD4 is a major genetic factor for the development of schizophrenia, analyses for moderate predisposing effects are still of significant interest. We performed a study examining differences in allele frequencies of 4 different DRD4 polymorphisms in schizophrenia patients and age, sex, and ethnic origin matched controls. None of these 4 polymorphisms showed evidence for genetic association with schizophrenia, although a trend towards excess of the allele with 7 repeats in the (48)_n bp exon III polymorphism was observed. Complexities in the DRD4 genetic investigation and further analytic approaches are discussed. © 1995 Wiley-Liss, Inc.     

山西地区汉族人群六个短串联重复序列基因座的遗传多态性

目的 分析山西地区汉族D9S925、D11S2368、D14S608、D15S659、D17S1290、D20S470等6个短串联重复序列(short tandem repeat,STR)基因座的遗传多态性.方法 根据GenBank资料合成D9S925、D11S2368、D14S608、D17S1290、D20S470基因座引物,自行设计D15S659引物,对山西汉族194个无关个体DNA进行PCR扩增,3130型基因分析仪电泳分析,GeneMapper(R)3.2分析等位基因片段大小,测序后命名.结果 6个STR基因座基因型频率分布符合Hardy-Weinberg平衡(P＞0.05).6个STR基因座的多态性信息含量在0.750～0.860之间,杂合度在0.756～0.894之间,个体识别力在0.920～0.965之间,非父排除概率在0.519～0.784之间,累积非父排除率为0.9988,累积个体识别能力为0.99999998.结论 本次研究的6个STR基因座在山西汉族群体中等位基因频率分布均匀,多态性好,适用于法医学亲子鉴定及个人识别,可作为现有基因座的补充.     

Reduced visuospatial performance in children with the D2 dopamine receptor A1 allele

Previous studies suggest a reduced dopaminergic function in subjects with the A1 (minor) allele of the D2 dopamine receptor (DRD2) gene. To explore influences on visuospatial ability as a function of the DRD2 gene, 182 alcohol- and other drug-naive sons (age 10–14) of active alcoholic, recovered alcoholic, and nonalcoholic fathers were administered a visuospatial task (Benton's Judgment of Line Orientation Test) which makes minimal motoric/verbal demands. Visuospatial scores were lower for boys with the A1 allele and for sons of active alcoholics. A1-allele boys made more errors than A2 boys on all 11 of the template lines, with the effect being largest for the rightmost presentations. In contrast, the effect of family history for alcoholism was strongest on both right and left midquadrant presentations. Moreover, separate analyses of the two types of errors produced allele but not family history of alcoholism effects when the two lines were misjudged as farther apart than they actually were and family history but not allele effects where the two lines were misjudged as closer together. These results suggest that polymorphism of the DRD2 gene and family history of alcoholism are dissociable determinants of visuospatial ability and that visuospatial defects previously observed in alcoholics may, in part, be antecedent to their drinking behavior.