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1.
The dopamine D2 receptor (DRD2) gene has been proposed as a candidate gene underlying several psychiatric and neurologic disorders. The aim of the present study was to examine if selected polymorphisms in the DRD2 gene are associated with Parkinson's disease (PD). We determined the allelic frequencies for four polymorphisms located in the DRD2 gene in a sample of 135 patients with PD and 202 normal control subjects. No significant difference was observed in the allelic frequencies between patients with PD and control subjects with regard to the -141C Ins/Del and the Ser311/Cys311 variants. On the contrary, the A1 allele of the TaqIA polymorphism and the B1 allele of the TaqIB polymorphism were more frequent in patients with PD than in control subjects (control subjects: TaqIA A1 = 14.6%, TaqIB B1 = 10.6%; patients with PD: TaqIA A1 = 20.7%, TaqIB B1 = 17.4%). Patients carrying the A1 allele or the B allele had an increased risk of developing PD (TaqIA, odds ratio: 1.71, 95% confidence intervals: 1.08-2.73; TaqIB, odds ratio: 1.83, 95% confidence intervals: 1.12-3.02). The TaqIA and TaqIB polymorphisms were in strong linkage disequilibrium, suggesting that these two polymorphisms convey the same information about the risk of presenting with PD. Genetic variation in the DRD2 gene may influence the risk of developing PD, thus confirming that the DRD2 gene is a susceptibility locus for PD.  相似文献   

2.
The TaqIA1 allele of the dopamine receptor gene D2 (DRD2) has been associated with alcoholism, as well as with other addictive behaviours. The exact nature of how the presence of this allele can be a vulnerability factor in the development of alcoholism remains unclear. In this study we found that the presence in the DRD2 genotype of the TaqIA1 allele in Spanish alcoholics is associated with higher levels of urine homovanillic acid (HVA) when compared to patients homozygous for the TaqIA2 allele. A sample of 142 Spanish male alcoholic patients was split into 2 groups on the basis of the presence or absence of the A1 allele in their genotype. The urine sample was analyzed by high performance liquid cromatography (HPLC), and the concentration of homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA) and vanilylmandelic acid (VMA) was determined. We found a statistical difference in the concentration of HVA between the groups, that suggests this polymorphism could be related to the variance of urine HVA levels.  相似文献   

3.
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。  相似文献   

4.
Polymorphisms in the dopamine D2 receptor gene (DRD2) have repeatedly been associated with schizophrenia. Recently, the C957T polymorphism (rs6277), which alters mRNA stability and dopamine-induced upregulation of DRD2 expression in cell cultures and DRD2 mRNA translation in vitro, was tested for an association with the disease. Frequency of the C allele, corresponding to a normal wild-type level of expression, was higher in patients compared to controls, and that of the T allele was lower. To replicate and extend previous findings, we conducted an association study of the C957T polymorphism and two additional SNPs (C939T and TaqIA) in 311 patients with a DSM-IV diagnosis of schizophrenia and 364 mentally healthy people from the Russian population as controls. The results of our study confirmed the association between the C957T polymorphism and schizophrenia. Consistent with previous findings, frequency of the C allele and the CC genotype were higher in patients compared to the control group (p = 0.002). Meta-analysis of total 5 samples also suggests significant allelic association. The distribution of C939T genotypes in the case sample was significantly different from that of the controls: in the case sample, the TT genotype frequency was higher compared to the combined frequency of CT and CC genotypes (p = 0.002). Though no association was found between the TaqIA polymorphism and schizophrenia, a haplotype-wise analysis revealed a lower frequency of the T–C (C957T–TaqIA) haplotype in patients (p = 0.02). In conclusion, our findings provide additional evidence for an association between the C957T polymorphism and schizophrenia.  相似文献   

5.
In humans, the A1 (T) allele of the dopamine (DA) D2 receptor/ankyrin repeat and kinase domain containing 1 (DRD2/ANKK1) TaqIA (rs1800497) single nucleotide polymorphism has been associated with reduced striatal DA D2/D3 receptor (D2/D3R) availability. However, radioligands used to estimate D2/D3R are displaceable by endogenous DA and are nonselective for D2R, leaving the relationship between TaqIA genotype and D2R specific binding uncertain. Using the positron emission tomography (PET) radioligand, (N‐[11C]methyl)benperidol ([11C]NMB), which is highly selective for D2R over D3R and is not displaceable by endogenous DA, the current study examined whether DRD2/ANKK1 TaqIA genotype predicts D2R specific binding in two independent samples. Sample 1 (n = 39) was composed of obese and nonobese adults; sample 2 (n = 18) was composed of healthy controls, unmedicated individuals with schizophrenia, and siblings of individuals with schizophrenia. Across both samples, A1 allele carriers (A1+) had 5 to 12% less striatal D2R specific binding relative to individuals homozygous for the A2 allele (A1?), regardless of body mass index or diagnostic group. This reduction is comparable to previous PET studies of D2/D3R availability (10–14%). The pooled effect size for the difference in total striatal D2R binding between A1+ and A1? was large (0.84). In summary, in line with studies using displaceable D2/D3R radioligands, our results indicate that DRD2/ANKK1 TaqIA allele status predicts striatal D2R specific binding as measured by D2R‐selective [11C]NMB. These findings support the hypothesis that DRD2/ANKK1 TaqIA allele status may modify D2R, perhaps conferring risk for certain disease states.  相似文献   

6.
To test the importance of the dopamine D2 receptor (DRD2) region in nicotine dependence, 150 smokers and 228 controls were genotyped for the DRD2 C957T, -141delC and ANKK1 TaqIA polymorphisms (rs6277, rs1799732 and rs1800497, respectively). The -141delC SNP did not show any association but both the C957T and TaqIA SNPs showed association at the allele, genotype, haplotype and combined genotype levels. The 957C/TaqI A1 haplotype was more than 3.5 times as likely to be associated with nicotine dependence compared with the 957T/TaqI A1 haplotype (P=0.003). Analysis of the combined genotypes of both SNPs revealed that individuals who were homozygous for the 957C-allele (CC) and had either one or two copies of the TaqI A1-allele were 3.3 times as likely to have nicotine dependence compared to all other genotype combinations (P=0.0003) and that these genotypes accounted for approximately 13% of the susceptibility to nicotine addiction in our population. Our findings suggest that the DRD2 C957T polymorphism and the ANKK1 TaqIA polymorphism are key contributors to the genetic susceptibility to nicotine dependence.  相似文献   

7.
A number of genetic polymorphisms are related to individual differences in cognitive performance. Striatal dopamine (DA) functions, associated with cognitive performance, are linked to the TaqIA polymorphism of the DRD2/ANKK1 gene. In humans, presence of an A1 allele of the DRD2/ANKK1‐TaqIA polymorphism is related to reduced density of striatal DA D2 receptors. The resource‐modulation hypothesis assumes that aging‐related losses of neurochemical and structural brain resources modulate the extent to which genetic variations affect cognitive functioning. Here, we tested this hypothesis using functional MRI during long‐term memory (LTM) updating in younger and older carriers and noncarriers of the A1‐allele of the TaqIa polymorphism. We demonstrate that older A1‐carriers have worse memory performance, specifically during LTM updating, compared to noncarriers. Moreover, A1‐carriers exhibited less blood oxygen level‐dependent (BOLD) activation in left caudate nucleus, a region critical to updating. This effect was only seen in older adults, suggesting magnification of genetic effects on functional brain activity in aging. Further, a positive relationship between caudate BOLD activation and updating performance among non‐A1 carriers indicated that caudate activation was behaviorally relevant. These results demonstrate a link between the DRD2/ANKK1‐TaqIA polymorphism and neurocognitive deficits related to LTM updating, and provide novel evidence that this effect is magnified in aging. Hum Brain Mapp 36:1325–1334, 2015. © 2014 Wiley Periodicals, Inc.  相似文献   

8.
Little is known about the genetic factors that underlie the comorbidity between alcohol use disorder and antisocial personality disorder. Previous studies have associated both, dopaminergic and endocannabinoid systems to severe alcoholism with non-adaptive disrupted behaviours. In this work we have examined some gene variants involved in such systems in a sample of alcoholic patients to test whether there is a relationship with antisocial traits. The genetic analysis involved the genotyping of the single nucleotide polymorphism (SNP) TaqIA located nearby the DRD2 gene, the 10-repeat allele of a variable number tandem repeats (VNTR) of the SLC6A3 gene, the C385A FAAH SNP and the 3'-UTR microsatellite of CNR1 gene. The clinical study was performed in 137 Spanish alcohol dependent males. Antisocial Personality Disorder (DSM-IV) diagnosis was made by applying the International Personality Disorder Examination, and psychopathic traits were evaluated by the Hare's Psychopathy Checklist revised (PCL-R). The genotype distribution indicates there is a relationship between the TaqIA SNP, CNR1 and FAAH genes and PCL-R's Factor 1 in alcoholic patients. This relationship seems to be additive and independent and might be responsible for 11.4% of the variance in this PCL-R subscale. Our results suggest the implication of the dopaminergic and endocannabinoid systems in those processes leading to the comorbidity of alcoholism and antisocial behaviour.  相似文献   

9.
We analysed the impact of the TaqI A1 allele of the D2 dopamine receptor gene on the risk for alcoholism, trying to depict three explanations frequently proposed to explain discrepancies in association and linkage studies: that the A1 allele may act as a marker rather than as a vulnerability factor, that stratification biases and unevaluated controls may explain positive results, and that the A1 allele is modifying the phenotype rather than increasing the risk for alcoholism. We thus tested another (dinucleotide STRP) marker within the DRD2 gene, selected a new homogenous sample of 113 alcoholic patients and 49 unaffected controls strictly matched for ethnic origins, and systematically assessed both samples with a semi-structured interview to detect (in both samples) alcohol dependence, but also such related traits as specificities of complications. The frequency of the A1 allele was not significantly different between alcoholics and controls but when comparing different subgroups of alcoholics, the A1 allele was significantly more frequent in alcoholic patients with somatic complications (OR = 3.00, CI[1.37-6.62]), social and professional complications (OR = 2. 72, CI[1.25-5.90]), or with co-morbid dependence (OR = 2.88, 95% IC [1.16-7.15]). The association for co-morbid dependence and somatic complications was also positive when taking into consideration both STRP and TaqIA polymorphisms. The A1 allele does not increase the risk for alcoholism per se in our sample, but may be involved in a related trait which is partially dependent on the diagnosis of alcoholism, through a disequilibrium with another close mutation.  相似文献   

10.
Little is known about the genetic factors that underlie the comorbidity between alcohol use disorder and antisocial personality disorder. Previous studies have associated both, dopaminergic and endocannabinoid systems to severe alcoholism with non-adaptive disrupted behaviours. In this work we have examined some gene variants involved in such systems in a sample of alcoholic patients to test whether there is a relationship with antisocial traits. The genetic analysis involved the genotyping of the single nucleotide polymorphism (SNP) TaqIA located nearby theDRD2 gene, the 10-repeat allele of a variable number tandem repeats (VNTR) of theSLC6A3 gene, the C385AFAAH SNP and the 3′-UTR microsatellite ofCNR1 gene. The clinical study was performed in 137 Spanish alcohol dependent males. Antisocial Personality Disorder (DSM-IV) diagnosis was made by applying the International Personality Disorder Examination, and psychopathic traits were evaluated by the Hare’s Psychopathy Checklist Revised (PCL-R). The genotype distribution indicates there is a relationship between the TaqIA SNP,CNR1 andFAAH genes and PCL-R’s Factor 1 in alcoholic patients. This relationship seems to be additive and independent and might be responsible for 11.4% of the variance in this PCL-R subscale. Our results suggest the implication of the dopaminergic and endocannabinoid systems in those processes leading to the comorbidity of alcoholism and antisocial behaviour.  相似文献   

11.
The objective of the study was to test the hypotheses that humans with genotypes putatively associated with low dopamine (DA) signaling capacity, including the TaqIA A1 allele, DRD2-141C Ins/Ins genotype, DRD4 7-repeat or longer allele, DAT1 10-repeat allele, and the Met/Met COMT genotype, and with a greater number of these genotypes per a multilocus composite, show less responsivity of reward regions that primarily rely on DA signaling. Functional magnetic resonance imaging (fMRI) paradigms were used to investigate activation in response to receipt and anticipated receipt of palatable food and monetary reward. DNA was extracted from saliva using standard methods. Participants were 160 adolescents (mean age = 15.3 years, SD = 1.07 years; mean body mass index = 20.8, SD = 1.9). The main outcome was blood oxygenation level-dependent activation in the fMRI paradigms. Data confirmed that these fMRI paradigms activated reward, attention, somatosensory, and gustatory regions. Individuals with, versus without, these five genotypes did not show less activation of DA-based reward regions, but those with the Met/Met versus the Val/Val COMT genotype showed less middle temporal gyrus activation and those with the DRD4-L versus the DRD4-S genotype showed less middle occipital gyrus activation in response to monetary reward. Critically, the multilocus composite score revealed that those with a greater number of these genotypes showed less activation in reward regions, including the putamen, caudate, and insula, in response to monetary reward. The results suggest that the multilocus genetic composite is a more sensitive index of vulnerability for low reward region responsivity than individual genotypes.  相似文献   

12.
The density of striatal dopamine D2 receptors has been shown to vary considerably among healthy subjects. This variability might be due to genetic or environmental factors. In the present analysis we searched for relationships between dopamine D2 receptor gene (DRD2) polymorphisms and striatal dopamine D2 receptor density in vivo, as measured by positron emission tomography and [11C]raclopride in 56 healthy subjects. There was a significant association between presence of a putative functional DRD2 promoter allele (-141C Del) and high striatal dopamine receptor density (t= 2.32, P= 0.02). In agreement with some previous studies the presence of the DRD2 TaqIA1 allele was associated with measures of low dopamine receptor density (t=2.58, P=0.01). Also the DRD2 TaqIB1 allele was associated with low dopamine receptor density (t= 2.58, P= 0.01) wheras there was no significant relationship between another common silent intronic DRD2 short tandem repeat polymorphism (STRP) and striatal dopamine D2 receptor density. The results suggest that DRD2 genotypes may participate differentially in the regulation of striatal dopamine D2 receptor density in healthy human subjects. The results should be interpreted with caution because of the limited sample size.  相似文献   

13.
CONTEXT: Dopamine receptor-mediated pathways play critical roles in the mechanism of addiction. However, associations of the D(2) dopamine receptor gene (DRD2) with substance abuse are controversial. OBJECTIVE: To determine whether susceptibility sites resided at DRD2. DESIGN: Haplotype-based case-control analysis of 2 distinct populations using 10 single nucleotide polymorphisms (SNPs) with heroin dependence. SETTING: Universities of Mainz and Bonn, Germany, and 3 local hospitals in southwestern China.Patients Cases and control subjects recruited from China (486 cases, 313 controls) and Germany (471 cases, 192 controls). INTERVENTIONS: Genotyping for 10 SNPs by 5'-exonuclease fluorescence assays. The D' value of linkage disequilibrium and haplotypes were generated by the expectation-maximization algorithm. MAIN OUTCOME MEASURES: Genotype, allele, and haplotype frequencies were compared between cases and controls by chi(2) tests constructed for each population. An additional 32 SNPs randomly distributed in the genome were genotyped for detecting population admixture in the 2 populations. RESULTS: A haplotype block of 25.8 kilobases (kb) was defined by 8 SNPs extending from SNP3 (TaqIB) at the 5' end to SNP10 site (TaqIA) located 10 kb distal to the 3' end of the gene. Within this block, specific haplotype cluster A (carrying TaqIB1 allele) was associated with a high risk of heroin dependence in Chinese patients (P = 1.425 x 10(-22); odds ratio, 52.80; 95% confidence interval, 7.290-382.5 for 8-SNP analysis). A putative recombination "hot spot" was found near SNP6 (intron 6 ins/del G), creating 2 new daughter haplotypes that were associated with a lower risk of heroin dependence in Germans (P = 1.94 x 10(-11) for 8-SNP analysis). There was no evidence of population stratification in either population. CONCLUSIONS: These results strongly support a role of DRD2 as a susceptibility gene with heroin dependence in Chinese patients and was associated with low risk of heroin dependence in Germans.  相似文献   

14.
目的 研究抗癫痫药物引致的皮肤不良反应和人白细胞抗原HLA-B*1502基因的关联性.探讨抗癫痫药物的个体化治疗. 方法 广州医学院第二附属医院癫痫门诊自2007年1月至2008年5月共收治癫痫患者31例.其中应用卡马两平(CBZ)引致皮肤不良反应13例[Stevens-Johnson综合征(SJS)6例、轻度斑丘疹(MPE)7例],无皮肤不良反应15例,应用拉莫三嗪(LTG)引致MPE 3例.采用顺序特异性引物聚合酶链反应(PCR-SSP)检测以上患者和未服用过CBZ或LTG的30例正常对照者的HLA-B*1502基因分型. 结果 HLA-B*1502基因型阳性例数和基因频率分别为:CBZ引致SJS组6例(6/6,100%),CBZ引致MPE组4例(4/7,57%),LTG引致MPE组I例(1/3,33%),无皮肤不良反应组1例(1/15,7%),正常对照组3例(3/30,10%).CBZ引致SJS组、CBZ引致MPE组患者HLA-B*1502基因型阳性率均高于正常对照组和无皮肤不良反应组,差异均有统计学意义(P<0.05). 结论 CBZ导致的皮肤不良反应与HLA-B*1502基因型有关.  相似文献   

15.
Association between attention deficit hyperactivity disorder (ADHD) and the 10-repeat allele of a polymorphism (a 40 bp variable number of tandem repeats) in the dopamine transporter gene (DAT1) has been reported by several groups. In this study, we examined whether either allele of the DAT1 core promoter -67 functional polymorphism is associated with ADHD in a case/control study. The allele and genotype frequencies of the polymorphism were studied in 110 patients and 120 controls, which were matched on the basis of sex, age and ethnicity. The genotype frequencies in the patients group were as follows: AA 19.2%; AT 65.2%; TT 15.4% vs. the genotype frequencies in the control group: AA 47.5%; AT 43.3%; TT 9.2% [chi2=20.73, df=2, P相似文献   

16.
The 7-repeat allele of the dopamine receptor D4 gene (DRD4) and the 10 repeat allele of the dopamine transporter gene (DAT1) have shown association and linkage with symptoms of attention deficit hyperactivity disorder (ADHD) in childhood. The parents of ADHD children (clinic group, n = 80 fathers and 107 mothers) and control children (control group, n = 42 fathers and 51 mothers) were the focus of this study. These parents reported retrospectively on their level of ADHD Inattention and Conduct Disorder symptoms in adolescence. In analyses of the relation of symptom levels to the DRD4 and DAT1 genotypes, fathers possessing the 7 repeat DRD4 allele had greater levels of both inattention and conduct disorder symptoms. Mothers with the 10/10 genotype had higher levels of inattention symptoms. Thus, genetic associations found in children may be replicable in their parents.  相似文献   

17.
The C957T polymorphism of the human dopamine D2 receptor gene (DRD2) regulates DRD2 availability in striatum in vivo. Specifically, the T allele predicts high DRD2 availability in healthy volunteers (T/T>T/C>C/C). However, this finding was unexpected as in vitro the T allele is associated with a decrease in DRD2 mRNA stability and synthesis of the receptor through a putative alteration in the receptor mRNA folding. To elucidate further how changes in DRD2 density (Bmax) and affinity (KD) contribute to the differences in DRD2 availability between the C957T genotypes, we studied these parameters separately in a sample of 45 healthy volunteers. The subjects had two PET scans with [11C]raclopride (high and low specific radioactivity scans) for the estimation of Bmax and KD, and were genotyped for the C957T. Moreover, the role of the related and previously studied functional TaqIA polymorphism of ankyrin repeat and kinase domain containing 1 (ANKK1) gene was reassessed for comparative purposes. The results indicate that the C957T increased binding potential by decreasing DRD2 KD (C/C>C/T>T/T), while Bmax was not significantly altered. These preliminary findings indicate that the C957T genotype‐dependent changes in DRD2 availability are driven by alterations in receptor affinity and putatively in striatal dopamine levels. This mechanism seems to differ from that observed previously for the ANKK1 gene TaqIA polymorphism, where the minor allele (A1) affects DRD2 availability predominantly by changing Bmax. The hypothesis that the two SNPs may have independent effects on dopamine neurotransmission needs to be further tested. Synapse 63:907–912, 2009. © 2009 Wiley‐Liss, Inc.  相似文献   

18.
J Wang  Z L Liu  B Chen 《Neurology》2001,56(12):1757-1759
The authors investigated the association between dopamine receptor D2, D3 gene polymorphisms, and the risk of developing motor fluctuations in PD. DRD3 BalI and MspI polymorphisms were not associated with risk of developing motor fluctuations. However, the genotypic distribution of DRD2 TaqIA polymorphism was significantly different in motor fluctuators and nonmotor fluctuators. These findings suggest that DRD2 TaqIA polymorphism may be associated with an increased risk for developing motor fluctuations in PD.  相似文献   

19.
An association between schizophrenia and a rare perfect ten-repeat allele, K1p, of a tetranucleotide microsatellite polymorphism in the tyrosine hydroxylase gene has recently been reported. The rare allele was found only in schizophrenic patients. During treatment with antipsychotic drugs patients with the rare allele displayed lower plasma homovanillic acid (HVA) and 3-methoxy-4-hydroxyphenylglycol (MHPG) levels than those without. We examined Swedish schizophrenic patients (n = 117) and healthy control subjects (n = 76) for the same polymorphism. In contrast to the previous studies, the K1p frequency in patients (4 of 117) tended to be lower than among controls (9 of 76). With all six alleles (K1p, K1i, K2–5) considered there was a significant difference between schizophrenic patients and control subjects. There was no significant difference in HVA and MHPG levels in cerebrospinal fluid from a subset (n = 64) of control subjects with and without the rare allele. The discrepant results warrant further investigation of the tyrosine hydroxylase gene. Received: 5 June 1997 / Accepted: 12 December 1997  相似文献   

20.
OBJECTIVE: The relationship is examined of the dopamine D2 receptor (DRD2) polymorphism (TaqIA, TaqIB, -141 C Ins/Del) and the catechol-O-methyltransferase (COMT) polymorphism (A-278G, G158A) to the risk of antipsychotic-induced extrapyramidal symptoms (EPS) in schizophrenia and bipolar disorders. Participants comprised 80 cases presenting with EPS (Simpson-Angus Scale score >3) and 188 controls presenting without EPS (Simpson-Angus Scale score 相似文献   

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