HTR2A基因多态性与云南彝族酒精依赖关联性研究

目的：探讨酒精依赖和云南彝族5-羟色胺2A受体（HTR2A）基因多态之间的关系。方法：采用PCR-RFLP技术对330健康人（对照组）和110名酒精依赖者（病例组）的5-HT2A受体基因的遗传多态性进行检测。结果：在440例样本中共检测到2种等位基因A和G,三种基因型AA,AG,GG．三种基因型在对照组中频率分别是38．5％,55．8％,5．8％;在病例组中的频率分别是30％,63．6％,6．4％。结论：在云彝族人群中,HTR2A基因rs6311（A－1438G）位点与酒精依赖无显著关联,HTR2A基因rs6311（A-1438G）位点在云南汉族和云南彝族酒精依赖组中无显著差异,但是在健康对照组中存在关联性．     

多巴胺D2受体基因多态性位点与海洛因依赖的关系

目的:探讨多巴胺D2受体(Dopamine D2 receptors,DRD2)基因3'非翻译区Taq ⅠA、启动子区-141 Ins/Del 2个多态性位点和海洛因依赖的相关性.方法:采用聚合酶链反应-限制性片段长度多态(PCR-RFLP)技术检测320例海洛因依赖患者及300例健康对照组的TaqⅠA和-141 Ins/Del2个多态性位点的基因型.采用HaploView4.0及SPSS11.5软件分析这2个多态性位点的基因型、等位基因频率及组间差异.结果:DRD2基因Taq ⅠA位点的基因型及等位基因频率分布在海洛因依赖组与正常对照组存在显著性差异(p<0.01),海洛因依赖组TaqⅠA位点的等位基因A1频率显著高于正常对照组(x2=11.156,p=0.001,OR=1.463,95%CI=1.170～1.830);DRD2基因-141 Ins/Del位点的基因型及等位基因频率分布在海洛因依赖组与正常对照组之间无统计学差异(p<0.05).结论:DRD2基因TaqⅠA位点多态性可能与海洛因依赖有关,携带有TaqⅠA多态性位点A1等位基因的个体可能更容易对海洛因产生依赖.     

酒精依赖相关基因的遗传多态性

酒精依赖综合征受到复杂的生理、心理、个体遗传及环境等诸多因素的影响。有关研究已经证实了某些候选基因和酒精依赖密切相关。文章主要对与酒精依赖相关的酒精代谢关键酶(乙醇脱氢酶和乙醛脱氢酶以及细胞色素P450 2E1)基因以及调节神经递质作用的酶和受体(儿茶酚氧位甲基转移酶, 多巴胺受体D2、D4, μ阿片受体)基因遗传多态性研究作一综述。     

云南汉族酒精依赖综合征与COMT遗传多态性的关联研究

目的：研究儿茶酚胺氧位甲基转移酶（COMT）的不同基因型及等位基因频率在云南汉族酒精依赖综合征患者组和健康对照组的分布差异。方法：应用聚合酶链式反应．限制性片段长度多态性分析法,对COMT基因的rs2075507、rs737865、rs4680、rsl65599四个基因位点进行特异性扩增,限制性内切酶酶切分型。结果：上述4个候选基因中,COMT基因rs737865位点C／C基因型频率在健康对照组较酒依赖组高,其基因型分布在两组中有差异,且具有统计学意义（P〈0．05）。其余3个位点统计学分析均无显著性差异（P〉0．05）。单倍型分析：上述四个候选基因构建出12种主要单倍型（每种单倍型在对照组和酒依赖组中的频率至少有一个大于1％）,单倍型A—C—A—A有可能是云南汉族酒精依赖发生的一种危险因子（OR：2．865,P=0．003347）。连锁不平衡分析显示：云南汉族人群中,COMT基因的rs2075507和rs737865之间存在着强连锁（D〉0．8）。结论：在云南汉族人群中,COMT基因rs2075507、rs4680和rs165599位点与酒依赖无关联性,rs737865C／C基因型可能是酒精依赖的保护因子,可能降低嗜酒的发生率。单倍型A-C-A-A有可能是云南汉族酒精依赖发生的一种危险因子。云南汉族人群中,COMT基因的rs2075507和rs737865之间存在着强连锁。     

云南汉族酒精依赖综合征与COMT遗传多态性的关联研究

目的:研究儿茶酚胺氧位甲基转移酶(COMT)的不同基因型及等位基因频率在云南汉族酒精依赖综合征患者组和健康对照组的分布差异。方法:应用聚合酶链式反应-限制性片段长度多态性分析法,对COMT基因的rs2075507、rs737865、rs4680、rs165599四个基因位点进行特异性扩增,限制性内切酶酶切分型。结果:上述4个候选基因中,COMT基因rs737865位点C/C基因型频率在健康对照组较酒依赖组高,其基因型分布在两组中有差异,且具有统计学意义(P<0.05)其余3个位点统计学分析均无显著性差异(P>0.05)。单倍型分析:上述四个候选基因构建出12种主要单倍型(每种单倍型在对照组和酒依赖组中的频率至少有一个大于1%),单倍型A-C-A-A有可能是云南汉族酒精依赖发生的一种危险因子(OR:2.865,P=0.003347)连锁不平衡分析显示:云南汉族人群中,COMT基因的rs2075507和rs737865之间存在着强连锁(D>0.8)结论:在云南汉族人群中,COMT基因rs2075507、rs4680和rs165599位点与酒依赖无关联性,rs737865C/C基因型可能是酒精依赖的保护因子,可能降低嗜酒的发生率。单倍型A-C-A-A有可能是云南汉族酒精依赖发生的一种危险因子云南汉族人群中,COMT基因的rs2075507和rs737865之间存在着强连锁。     

云南汉族人群5-羟色胺转运体基因启动子区多态性与酒精依赖的相关性

为了探讨云南汉族人群中5-羟色胺转运体基因启动子区多态性(5-HTTLPR)与酒精依赖的关联性, 文章采用PCR扩增和DNA测序技术, 对云南地区118例酒精依赖患者和214例健康对照个体进行了5-HTTLPR的基因多态性分析。结果表明: 酒精依赖患者组和正常对照组的5-HTTLPR的基因型分布存在显著性差异, L/L和L/S基因的携带者人群嗜酒发生率显著低于S/S基因型人群(OR: 0.581, P=0.026)。S和L等位基因频率在两组间无统计学差异(χ²=2.594, P=0.107), 但其分布存在种族差异性。因此, 云南地区人群中5-HTTLPR多态与酒精依赖存在相关性, L/L和L/S基因型可能是降低酒精依赖发病的影响因子之一。     

多巴胺D2受体基因TaqIB多态性与酒依赖的关系

目的:探讨汉族人群中多巴胺D2受体(DRD2)基因TaqIB多态性与酒依赖的相关性.方法:采用聚合酶链式反应-限制性片断长度多态性(PCR-RFLP)技术,检测酒依赖组(80例)和对照组(95例)的DRD2基因TaqIB多态性的基因型和等位基因频率.结果:酒依赖组和时照组的DRD2基因TaqIB多态性的基因型和等位基因频率有显著性差异,等位基因B2的携带者显著降低其嗜酒的发生率(OR:1.636,P＜0.05).结论:本研究提示,在汉族人群中DRD2基因TaqIB多态性与酒依赖存在相关性,TaqIB2等位基因可能是降低酒依赖发病的影响因子.     

多巴胺D4受体基因启动子区多态性与精神分裂症的相关性

目的:探讨多巴胺D4受体(Dopaminc D4 receptor,DRD4)基因启动子区的3个功能多态性与精神分裂症是否存在相关性.方法:严格按照诊断标准,选取无亲缘关系的精神分裂症患者220例,健康对照组200例提取基因组DNA,采用聚合酶链反应及等位基因特异性扩增技术检测DRD4基因启动子区-521C/T、-616C/G和-1240L/S 3个功能位点的基因型,采用HaploView4.0及SPSS11.5软件分析各位点基因型、等位基因频率及组间差异.结果:DRD4基因-1240L/S的基因型及等位基因频率分布在精神分裂症与正常对照组存在显著性差异(p<0.05).DRIM基因启动子区-521C/T和-616C/G位点的基因型及等位基因频率分布在精神分裂症组与正常对照组无统计学差异(p>0.05).结论:DRD4基因-1240L/S多态性与精神分裂症相关联,携带有-1240L/S多态性住点L等住基因的个体可能更容易患精神分裂症.     

多巴胺D4受体基因启动子区功能多态性与海洛因依赖的相关性研究

目的:探讨多巴胺D4受体(DRD4)基因启动子区的3个功能多态性位点与海洛因依赖的相关性.方法:严格按照诊断标准,选取无亲缘关系的海洛因依赖患者212例及健康对照组200例提取基因组DNA,采用聚合酶链反应及等位基因特异性扩增技术检测DRD4基因启动子区-521C/T、-616C/G、及-1240L/S 3个功能多态性位点的基因型,采用HaploView及SPSS11.5软件分析各位点基因型、等位基因频率及组间差异.结果:DRD4基因-521C/T的基因型及等位基因频率分布在海洛因依赖组与正常对照组存在显著性差异(p＜0.05).结论:多巴胺D4受体(DRD4)基因-521C/T多态性与海洛因依赖相关联,T等位基因可能是海洛因依赖的风险因子.     

TLR4基因多态性与感染性ARDS易感性的相关性研究

目的研究Toll样受体4(TLR4)基因Asp299Gly、Thr399Ile多态性与感染性急性呼吸窘迫综合征(ARDS)的关系。方法采用多聚酶链反应-限制性片段长度多态性(PCR-RFLP)方法,对40例感染性ARDS患者和50名健康人进行TLR4等位基因Asp299Gly和Thr399Ile的基因型检测。结果在感染性ARDS患者和健康体检者中,TLR4受体基因Asp299Gly、Thr399Ile两位点的基因型之间差异无统计学意义(χ2=0.043,P=0.635;χ2=0.071,P=0.583)。结论感染性ARDS患者的TLR4基因Asp299Gly和Thr399Ile多态性与感染性ARDS发病无显著相关性。     

Dopamine transporter (DAT1) and dopamine receptor D4 (DRD4) genotypes differentially impact on electrophysiological correlates of error processing

Recent studies as well as theoretical models of error processing assign fundamental importance to the brain's dopaminergic system. Research about how the electrophysiological correlates of error processing--the error-related negativity (ERN) and the error positivity (Pe)--are influenced by variations of common dopaminergic genes, however, is still relatively scarce. In the present study, we therefore investigated whether polymorphisms in the DAT1 gene and in the DRD4 gene, respectively, lead to interindividual differences in these error processing correlates. One hundred sixty participants completed a version of the Eriksen Flanker Task while a 26-channel EEG was recorded. The task was slightly modified in order to increase error rates. During data analysis, participants were split into two groups depending on their DAT1 and their DRD4 genotypes, respectively. ERN and Pe amplitudes after correct responses and after errors as well as difference amplitudes between errors and correct responses were analyzed. We found a differential effect of DAT1 genotype on the Pe difference amplitude but not on the ERN difference amplitude, while the reverse was true for DRD4 genotype. These findings are in line with predictions from theoretical models of dopaminergic transmission in the brain. They furthermore tie results from clinical investigations of disorders impacting on the dopamine system to genetic variations known to be at-risk genotypes.     

多巴胺D1受体基因多态性与注意缺陷多动障碍的相关性研究

目的:探讨多巴胺D1受体(Dopamine D1 receptor, DRD1)基因启动子区G-48A、外显子区T1403C两个SNP位点与注意缺陷多动障碍(attention deficit hyperactivity disorder,ADHD)的关联性.方法:选取87名ADHD患者和103名正常对照,提取基因组DNA,采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)技术检测G-48A和T1403C两个多态性位点的基因型,SPSS13.0软件分析各位点的等位基因及基因型频率.结果:DRD1的G-48A基因型及等位基因频率分布在ADHD和对照组之间有统计学差异(p<0.05),ADHD组中等位基因A频率显著高于正常组(p<0.05).T1403C位点基因型及等位基因频率在ADHD组与健康对照组无统计学差异.结论:DRD1基因G-48A多态性可能与ADHD的发病有关,携带有等位基因A的个体可能更容易患ADHD.T1403C多态性与ADHD的发病无明显相关性.     

云南彝族人群CYP2E1基因多态性与酒依赖的关联性研究

目的：探讨云南彝族人群中的酒精依赖患者和云南彝族人群中健康人在CYP2E1基因的一个SNP（Rs3813867）的等位基因和基因型频率的不同,试图找出酒依赖的危险基因,比较它与其他人群之间在CYP2E1PstI位（rs3813867）基因多态性的不同。方法：对110个酒精依赖者和330名健康的志愿者不喝酒（对照组）的CYP2E1PstI位的多态性,等位基因频率和基因型频率进行测定。采用PCR—RFLP方法进行基因分型。结果：CYP2 E1 Psfl位的多态性,等位基因频率和基因型频率是相似的在酒精依赖者和对照组（72．7％vs72．1％,C1／C1）,（25．5％vs25．8％,C1／C2）,（1．8％vs2．1％为C1／C2）和（85．5％vs85％c1的）,（14．5％VSl5％为c2）。结论：CYP2E1的基因型和等位基因分布在酒精依赖组和对照组之间没有显着性差异（P〉0．05）,在这两个民族在AD组和对照组基因型分布有差异（P〈0．001）。     

Dopamine D1, D2, D3 Receptors,Vesicular Monoamine Transporter Type-2 (VMAT2) and Dopamine Transporter (DAT) Densities in Aged Human Brain

The dopamine D₁, D₂, D₃ receptors, vesicular monoamine transporter type-2 (VMAT2), and dopamine transporter (DAT) densities were measured in 11 aged human brains (aged 77–107.8, mean: 91 years) by quantitative autoradiography. The density of D₁ receptors, VMAT2, and DAT was measured using [³H]{"type":"entrez-protein","attrs":{"text":"SCH23390","term_id":"1052733334","term_text":"SCH23390"}}SCH23390, [³H]dihydrotetrabenazine, and [³H]WIN35428, respectively. The density of D₂ and D₃ receptors was calculated using the D₃-preferring radioligand, [³H]WC-10 and the D₂-preferring radioligand [³H]raclopride using a mathematical model developed previously by our group. Dopamine D₁, D₂, and D₃ receptors are extensively distributed throughout striatum; the highest density of D₃ receptors occurred in the nucleus accumbens (NAc). The density of the DAT is 10–20-fold lower than that of VMAT2 in striatal regions. Dopamine D₃ receptor density exceeded D₂ receptor densities in extrastriatal regions, and thalamus contained a high level of D₃ receptors with negligible D₂ receptors. The density of dopamine D₁ linearly correlated with D₃ receptor density in the thalamus. The density of the DAT was negligible in the extrastriatal regions whereas the VMAT2 was expressed in moderate density. D₃ receptor and VMAT2 densities were in similar level between the aged human and aged rhesus brain samples, whereas aged human brain samples had lower range of densities of D₁ and D₂ receptors and DAT compared with the aged rhesus monkey brain. The differential density of D₃ and D₂ receptors in human brain will be useful in the interpretation of PET imaging studies in human subjects with existing radiotracers, and assist in the validation of newer PET radiotracers having a higher selectivity for dopamine D₂ or D₃ receptors.     

Population Migration and the Variation of Dopamine D4 Receptor (DRD4) Allele Frequencies Around the Globe

This article reports an association between the variation of dopamine D4 receptor (DRD4) allele frequencies around the globe and population migration patterns in prehistoric times. After compiling existing data on DRD4 allele frequencies of 2,320 individuals from 39 populations and on the migration pattern of these groups, we found that, compared to sedentary populations, migratory populations showed a higher proportion of long alleles for DRD4. The correlation between macro-migration (long-distance group migration) and the proportion of long alleles of DRD4 was .85 (p < .001), and that between micro-migration (sedentary vs. nomadic settlement) and the proportion of long alleles was .52 (p = .001). We discussed the adaptive value of long alleles of DRD4—a genetic trait that has been linked in some studies to the personality trait of novelty-seeking and to hyperactivity— in migratory societies and the possibility of natural selection for a migration gene.