多巴胺D2,D3受体基因多态性与原发性震颤遗传易患性的相关研究

原发性震颤(ET)是一种其病因与多种因素相关、较常见的运动障碍性疾病,遗传因素是病因之一.研究证实ET与帕金森病(PD)是相关联的疾病,二者的震颤发生机制类似,均与中枢多巴胺能神经系统功能失调相关.为探讨多巴胺D2,D3受体基因多态与ET遗传易患的相关性,采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)技术,首次检测80例无血缘相关的ET患者与100例正常对照DRD2基因Taq Ⅰ,DRD3基因Msp Ⅰ位点突变,比较ET与正常人之间的多态性频率的差异.DRD2基因Taq Ⅰ位点及DRD3基因Msp Ⅰ位点等位基因的基因型、基因频率分布在ET与正常对照无显著差异.DRD2基因Taq Ⅰ与DRD3基因Msp Ⅰ位点多态性可能与ET的遗传易患性无关.     

多巴胺D2，D3受体基因多态性与原发性震颤遗传易患性的相关研究

原发性震颤 (ET)是一种其病因与多种因素相关、较常见的运动障碍性疾病 ,遗传因素是病因之一。研究证实ET与帕金森病 (PD)是相关联的疾病 ,二者的震颤发生机制类似 ,均与中枢多巴胺能神经系统功能失调相关。为探讨多巴胺D2 ,D3受体基因多态与ET遗传易患的相关性 ,采用聚合酶链反应 限制性片段长度多态性(PCR RFLP)技术 ,首次检测 80例无血缘相关的ET患者与 10 0例正常对照DRD2基因TaqⅠ ,DRD3基因MspⅠ位点突变 ,比较ET与正常人之间的多态性频率的差异。DRD2基因TaqⅠ位点及DRD3基因MspⅠ位点等位基因的基因型、基因频率分布在ET与正常对照无显著差异。DRD2基因TaqⅠ与DRD3基因MspⅠ位点多态性可能与ET的遗传易患性无关。     

多巴胺D3受体基因Ser9Gly多态性与阿立哌唑及利培酮治疗效应的关联研究

目的比较阿立哌唑与利培酮治疗女性首发精神分裂症患者的疗效和血浆催乳素水平变化及其与多巴胺D3受体(DRD3)基因Ser9Gly(rs6280)多态性的关联。方法选择完成8周阿立哌唑或利培酮治疗的女性首发精神分裂症患者各60例,于治疗前和治疗8周后分别评测阳性与阴性症状量表(positive and negativesymptom scale,PANSS)。采用放射免疫法检测血浆催乳素水平,DNA测序技术检测DRD3基因Ser9Gly多态性,分析DRD3基因Ser9Gly多态性与两药疗效及血浆催乳素变化的关联。结果治疗8周后,两组PANSS减分率的差异无统计学意义[(59.79±23.48)vs.(63.30±22.66),P>0.05],但利培酮组血浆催乳素的变化值高于阿立哌唑组[(26.92±9.48)vs.(-25.25±8.07),P<0.05]。利培酮组中C等位基因携带者的血浆催乳素的增加明显高于未携带者[(52.48±27.01)ng/mL vs(36.07±17.46),P<0.05];而阿立哌唑组中未见此差异[(-23.27±8.36)vs.TT(-26.05±8.11),P>0.05]。两组8周后PANSS减分率(%)与DRD3基因Ser9Gly的差异均无统计学意义:阿立哌唑组[CC+CT(57.83±19.94)vs.TT(56.84±18.46),P>0.05];利培酮组[CC+CT(53.94±21.08)vs.TT(60.38±19.37),P>0.05]。结论阿立哌唑治疗女性首发精神分裂症疗效与利培酮相当,但引起血浆催乳素水平变化的幅度较小;利培酮引起血浆催乳素水平增加可能与DRD3基因Ser9Gly多态性有关联。     

双相情感障碍与DRD3、DRD2和COMT基因多态性的关联分析

目的　探索多巴胺D3受体 (DRD3)、多巴胺D2受体 (DRD2 )和儿茶酚氧位甲基转移酶 (COMT)基因多态性与双相情感障碍的关系。方法　使用病例 对照的关联分析方法 ,对 10 5名双相情感障碍患者和 12 8名对照者之DRD3、DRD2和COMT的多态性进行检测 ,并进行关联分析。结果　DRD3等位基因在两组间的分布有显著性差异 (χ2 =5 77,P =0 0 2 ) ,Logistic多元回归分析发现基因型 1/ 1和 2 / 2在两组间分布的有显著性差异 (P =0 0 36 ,OR=5 72 7) ,等位基因分析也有显著性差异 (P =0 0 2 2 ,OR =6 786 ) ;DRD2和COMT基因型和等位基因的分布在两组间无显著性差异 (χ2 =1 983,P =0 37/ χ2 =1 6 7,P =0 4 1;χ2 =0 2 16 ,P >0 0 5 / χ2 =0 14 3,P >0 0 5 ) ;将DRD3和DRD2共同分析时发现OR值升高 (OR =6 6 97)。结论　DRD3基因多态性与双相情感障碍有关联 ,且与DRD2有协同作用。     

精神分裂症与多巴胺D4受体基因及载脂蛋白E基因的关联分析

目的　探讨上海地区汉族人群载脂蛋白E(apoE)基因、多巴胺D4 受体 (DRD4)基因与精神分裂症的易患性、患者的性别、发病年龄以及病程之间的关系。方法　应用聚合酶链反应扩增技术及限制性片段长度多态性对 80例精神分裂症患者和 80名正常人分别测定apoE、D4基因型和等位基因。结果　 (1 )患者组apoE等位基因ε2 频率明显高于对照组 ,与精神分裂症呈显著正关联 [相对危险度 (RR) =2 0 1 ,P <0 0 5] ;而且患者组男性等位基因ε2 频率明显高于对照组男性 ,与精神分裂症呈显著正关联 (RR =8 5l,P <0 0 5)。 (2 )DRD4基因与精神分裂症无关联 ,但是发病年龄与A2 ,A4等位基因及性别与 4/ 4基因型有关联 (P <0 0 5) ;(3)患者组与对照组携带ε4 与非携带ε4 间比较 ,DRD4基因的基因型和等位基因频率均无差异。患者组和对照组的组内携带ε4 与非携带ε4 间比较的差异均有显著性 ,对照组携带ε4 组的DRD4基因型 4/ 4 (85 % )和等位基因A4(89% )频率均明显高于非携带ε4组 (55 % ,67% ) ,而非携带ε4 组的等位基因A2 (2 9% )频率高于携带ε4 组 (1 2 % ) ;患者组非携带ε4 组的DRD4基因型 2 / 2 (1 3 % )和等位基因A2 (2 4 % )频率均高于携带ε4 组 (0 % ,8% )。结论　 (1 )apoE基因可影响精神分裂症患者的易患性     

多巴胺D3受体基因多态性与精神分裂症患者迟发性运动障碍的关联分析

目的　观察广州地区汉族伴或不伴迟发性运动障碍 (TD)的精神分裂症患者多巴胺D3受体 (DRD3)基因Ser 9 Gly多态性分布 ,探讨DRD3基因Ser 9 Gly多态性与TD发生的关系。方法对 1 4 0例精神分裂症患者采用不自主运动评定量表 (AIMS)进行评定 ,其中 53例伴TD ,87例不伴TD。应用聚合酶链反应和限制性内切酶长度多态性方法 ,检测 1 4 0例患者的DRD3基因Ser 9 Gly多态性 ,并对DRD3各等位基因及基因型与精神分裂症患者的TD表型进行关联分析。结果　 (1 )TD组与无TD组患者基因型总体分布的差异无显著性 (χ2 =5 6 ,υ =2 ,P >0 0 5) ,等位基因频数分布的差异有显著性 (χ2 =5 1 1 ,υ =1 ,P <0 0 5)。 (2 )按性别分组后 ,在男性患者中 ,伴TD患者较不伴TD患者 1 / 1基因型和等位基因 1频率的差异有显著性 (χ2 =5 2 4 ,χ2 =5 0 6 ,P <0 0 5) ,等位基因 2的差异有显著性 (χ2 =5 0 6 ,P <0 0 5)。在女性患者中 ,DRD3各基因型及等位基因的频率的差异均无显著性 (P >0 0 5)。结论　DRD3基因Ser 9 Gly多态性可能与精神分裂症尤其是男性患者的TD关联     

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

目的:探讨多巴胺2(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(HPRL)的关联性。方法:92例女性精神分裂症患者给予利培酮或帕利哌酮治疗4周,于治疗前后测定血清PRL水平及治疗后的9-羟利培酮血药浓度;并检测所有受试者的D2受体基因Taq1A多态性。结果:HPRL组(治疗后PRL水平≥3 500 m IU/L者,n=30例)与LPRL组(治疗后PRL水平3 500m IU/L者,n=37例)Taq1A基因型等位基因频率组间差异无统计学意义(χ~2=1.73,P=0.42);Taq1A 3种基因型(A1/A1,A1/A2及A2/A2)患者血清PRL水平治疗后均明显增高,但治疗前后差值比较,组间差异无统计学意义(F=1.40,P=0.26)。结论:未发现D2受体基因Taq1A多态性与利培酮、帕利哌酮所致HPRL存在关联。     

多巴胺D2受体基因多态性与脑出血的相关性研究

目的 探讨多巴胺D2受体（DRD2）基因TaqI位点多态性与中国湖南地区汉族人群脑出血发病的相关性.方法 本研究筛选121例脑出血患者,匹配103例正常体检人群为对照,PCR-RFLP检测DRD2 TaqI基因多态性.结果 DRD2 TaqI三种基因型（A1A1,A1 A2,A2A2）频率及两种等位基因（A1,A2）频率在脑出血组和正常对照组分布的差异无统计学意义（P＞0.05）.脑出血组中高血压亚组、非高血压亚组及对照组三者两两比较DRD2 TaqI基因型频率分布的差异无统计学意义（P＞0.05）.Logistic回归调整了脑出血环境因素的影响后,DRD2 TaqI基因多态性仍与脑出血的无相关性（P＞0.05）.结论 DRD2 TaqI基因多态性可能与中国湖南地区汉族人群脑出血无关.     

多巴胺D2受体基因rs1800497多态性与精神分裂症的关联分析

目的 探讨中国汉族人群多巴胺D2受体（DRD2）基因rs1800497多态性与精神分裂症发病的关系及其与性别的关联性.方法 采用TaqMan法检测200例精神分裂症患者（患者组）和219名健康对照（对照组）DRD2基因rs1800497单核苷酸多态性（SNP）,并对等位基因、基因型频率进行比较.结果 患者组与对照组rs1800497等位基因分布和基因型分布差异均无统计学意义（P＞0.05）.患者组或对照组不同性别rs1800497等位基因分布和基因型分布差异均无统计学意义（P＞0.05）.男性患者组与对照组相比或女性患者组与对照组相比,rs1800497等位基因分布和基因型分布差异均无统计学意义（P＞0.05）.结论 中国汉族人群DRD2 rs1800497位点可能不是精神分裂症的易感位点.     

多巴胺D5受体基因多态性与精神分裂症的关联研究

目的　探讨昆明地区汉族人群多巴胺D5受体 (DRD5 )基因多态性与精神分裂症的关系。方法　对 79例精神分裂症患者 (患者组 )和 75名正常对照者 (对照组 )采用聚合酶链反应 (PCR)扩增DRD5基因二核苷酸多态性片段 ,并通过聚丙烯酰胺凝胶电泳对PCR扩增产物进行多态性分型鉴定。比较患者组与对照组DRD5基因各等位基因分布频率。结果　 ( 1)患者组与对照组之间等位基因分布的差异无显著性 ( χ2 =12 2 6 ,P >0 0 5 )。 ( 2 )女性患者比男性患者及对照组 14 0bp等位基因有更高的分布频率 ;与男性患者比较 ,相对危险度 (RR) =2 73( χ2 =5 33,P <0 0 5 ) ;与对照组比较 ,RR =2 0 1( χ2 =4 5 9,P <0 0 5 )。结论　未发现汉族人群中DRD5基因多态性与精神分裂症存在明显关联 ,但该基因多态性可能影响不同性别间的疾病易感性     

DRD2/ANKK1 TaqI A polymorphism affects corticostriatal activity in response to negative affective facial stimuli

DRD2/ANKK1 TaqI A polymorphism has been suggested to be involved in a reward-related psychiatric disorders. However, the effect of Dopamine receptor D2 (DRD2) on emotional processing has not been investigated yet. We investigated the possible relationship between DRD2/ANKK1 TaqI A polymorphism and corticostriatal response to negative facial stimuli using functional magnetic resonance imaging. All participants were genotyped with regard to the DRD2/ANKK1 TaqI A polymorphism. Our results suggest an association between the DRD2/ANKK1 TaqI A polymorphism and activations in the putamen, the anterior cingulate cortex, and amygdala in response to negative facial stimuli. Furthermore, molecular heterosis at the TaqI polymorphism of DRD2/ANKK1 may play an important role in affective regulation by corticostriatal pathway.     

多巴胺D3受体基因多态性与精神分裂症亚型及利培酮疗效相关性分析

目的探讨多巴胺D3受体(dopamine D3 receptor,DRD3)基因第一外显子丝氨酸9甘氨酸(Ser9Gly)多态性与精神分裂症临床亚型、药物疗效的关联.方法 241 例汉族首发精神分裂症患者,采用限制性片段长度多态性(restriction fragment length polymorphism,RFLP)技术测定基因型.分析判断基因多态性与精神分裂症的临床亚型、药物疗效的关联. 结果精神分裂症各亚型Ser9Gly等位基因分布存在显著性差异(p <0.05).利培酮疗效不同的患者间Ser9Gly等位基因多态性均无显著性差异. 结论 DRD3受体基因第一外显子Ser9Gly多态性可能与精神分裂症亚型相关,而与患者对药物的反应不相关.     

多巴胺2受体基因TaqIA多态性与美沙酮维持治疗海洛因依赖患者心理症状相关性研究

目的研究昆明市美沙酮维持治疗A门诊接受美沙酮维持治疗的汉族海洛因依赖者多巴胺D2受体基因TaqIA多态性与接受美沙酮维持治疗海洛因依赖患者心理症状的相关性,探讨影响病人治疗效果的遗传因素。方法对81例接受美沙酮维持治疗的海洛因依赖者实施SCL-90测试,应用聚合酶链式反应-限制性片段长度多态性（PCR-RFLP）技术,检测多巴胺D2受体基因TaqIA基因多态,比较不同基因型与SCL-90各因子的关系。结果 A1＋组（A1/A1,A1/A2）与A1-组（A2/A2）SCL-90各因子分无显著性差异。结论D2受体基因TaqIA多态性与美沙酮维持治疗海洛因依赖患者心理症状可能不存在相关性。     

多巴胺D2受体TaqI A多态性与海洛因渴求程度的关联分析

目的探讨多巴胺D2受体TaqI A多态性与线索诱发海洛因渴求程度的关系.方法 380名海洛因依赖者接受环境诱发渴求实验,用PCR-RFLP技术检测DRD2受体TaqI A多态性,比较不同基因型与线索暴露前后渴求程度的关系. 结果强制戒毒被试者基因型与暴露前后渴求程度未见显示差异(P＞0.05).自愿戒断被试者基因型与诱发后渴求分值、暴露前后渴求分差值的差异有显著性(F=4.523,P=0.012;F=3.936,P=0.021),A1/A1基因型被试者暴露后渴求程度高于A2/A2(P=0.027,P=0.019)和A1/A2(P=0.032,P=0.035)被试者.三者基因型在成瘾、加量和海洛因使用时间差异上有显著性(P=0.014,P=0.001,P=0.004).A1/A1基因型个体成瘾时间和加量时间小于A2/A2(P=0.007,P=0.001)和A1/A2(P=0.023,P=0.001)基因型个体,但吸毒时间大于A1/A2(P=0.003)和A2/A2(P=0.002)基因型个体. 结论 DRD2受体基因TaqI A多态性可能与环境诱发海洛因渴求程度易感性和成瘾、加量及毒品使用时间有关,A2+(A2/A2,A1/A2)基因型可能在海洛因依赖中起保护作用,而A2-(A1/A1)基因型则可能具有促进作用.     

Association of Parkinson disease age of onset with DRD2, DRD3 and GRIN2B polymorphisms

IntroductionDopamine and glutamate are crucial neurotransmitters in Parkinson disease (PD). While recent large meta-analyses reported that genetic variation of dopamine (DRD2, DRD3) and glutamine (NMDA, GRIN2B) neurotransmitter receptors was not associated with PD risk, they could conceivably influence PD phenotype. We studied the association of these receptor polymorphisms relating to PD age of onset.MethodsThere were 664 PD patients and 718 controls, all Caucasian, with stored DNA at Mayo Clinic, Jacksonville, Florida. Genotyping was performed for DRD2 (Taq 1A, rs1800497), DRD3 (rs6280), and NMDA (GRIN2B, rs7301328) polymorphisms with ABI Taqman assays. Single nucleotide polymorphism associations with age of onset were evaluated using dominant, recessive, and additive genotypic models.ResultsDRD3 variant carriers had an approximate 4.4-year decrease in mean age of onset when both copies of the minor allele were present (P = 0.0034) and an approximate 1.5-year decrease in mean age at onset for every additional minor allele (P = 0.023) (recessive and additive models, respectively). There was no association with age of onset for DRD2 or GRIN2B under any statistical model (all P ≥ 0.22).ConclusionsThe DRD3 (rs6280) polymorphism, but not DRD2 (Taq1A) or GRIN2B, influences younger PD age of onset in the US Caucasian population. Validation of these findings in larger studies with other ethnic groups is indicated.     

多巴胺D2受体基因的TaqI A多态性与迟发性运动障碍的关联分析

目的　研究多巴胺D2受体 (DRD2 )基因TaqIA多态性与精神分裂症伴迟发性运动障碍 (TD)的相关性。方法　使用异常不自主运动量表 (AIMS)评定精神分裂症患者有无TD及TD严重程度 ,并采用简明精神病评定量表 (BPRS)评定患者精神症状 ;应用聚合酶链反应 (PCR)—限制性片段长度多态性 (RFLP)法分析TD组和非TD组的DRD2基因的TaqIA等位基因频率和基因型分布。结果　DRD2基因TaqIA的等位基因频率和基因型分布在TD组与非TD组之间均无显著性差异 ,且不同基因型间的AIMS总分值也无显著性差异。结论　在中国汉族男性精神分裂症患者中DRD2基因的TaqIA多态性可能不是影响TD发生的主要危险因素。     

Dopamine DRD2 Taq I polymorphism associates with caudate nucleus volume and cognitive performance in memory impaired subjects

We studied the relationship among dopamine receptor D2 (DRD2) Taq I genetic polymorphism, caudate nucleus volumetry as measured using MRI and neuropsychological functions in 49 memory impaired older people. Compared with DRD2 A1 carriers, subjects homozygous for the DRD2 A2 allele performed poorer in a measure of general cognitive functioning (MMSE) and in long term verbal memory, and presented reduced left caudate nucleus volumes. Caudate nucleus atrophy correlated with cognitive measures influenced by the genetic polymorphism and with visual memory performance. Our findings suggest that among the aged with cognitive impairments, the homozygous status for the A2 allele of the DRD2 Taq I polymorphism is associated with diminished cognitive performance and increased atrophy in the striatum.     

DRD2 C957T polymorphism interacts with the COMT Val158Met polymorphism in human working memory ability

The C957T polymorphism in the dopamine D2 receptor (DRD2) gene and the Val158Met polymorphism in the Catechol-O-Methyl-Transferase (COMT) gene affect dopamine transmission and have been found to be associated with schizophrenia. Since DRD2 in mice and the COMT gene in humans modulate working memory, we examined the relationship and possible interaction of both polymorphisms to working memory performance in 188 healthy adults. Subjects having the DRD2 C/C allele showed the poorest performance in a word serial position test. Moreover, the effect of the C957T genotype was strengthened when interaction with the COMT Val158Met polymorphism was included in the analysis. We propose that an interaction of the DRD2 C957T and COMT Val158Met may be involved in the generation of some working memory deficits in schizophrenia.     

The DRD2 gene 957C>T polymorphism is associated with posttraumatic stress disorder in war veterans

Background: Variations in genes related to the dopaminergic pathway have been implicated in neuropsychiatric disorders such as schizophrenia, substance misuse, Alzheimer's disease and Post Traumatic Stress Disorder (PTSD). A single nucleotide polymorphism (SNP) (957C>T) and a deletion polymorphism (‐141delC) in the DRD2 gene and a SNP (Taq1A) in a gene directly downstream of DRD2 have all been implicated in dopamine functioning in the brain. Methods: To test the importance of these three polymorphisms in PTSD susceptibility, a genetic screen was performed in 127 war veterans diagnosed with PTSD and 228 control individuals without a history of PTSD. Results: No significant association was found between PTSD and the Taq1A or ‐141delC polymorphisms. However, a significant association was observed with PTSD and the 957C>T polymorphism. PTSD individuals were more likely to carry the C allele compared to the controls (P=0.021). Conclusions: Our findings suggest that the 957C>T polymorphism in the DRD2 gene is one of the genetic factors for susceptibility to PTSD. Depression Anxiety, 2009. © 2008 Wiley‐Liss, Inc.