多巴胺转运体基因多态性与Tourette综合征疗效的相关性研究

Objective To study the difference of dopamine transporter ( DAT1 )gene 40 bp variable number of tandem repeat ( VNTR ) genotype and allele frequency in TS patients with different curative effect in Chinese Han population. Methods In this study, the 40 bp polymorphism in the DAT1 gene was analyzed by using polymerase chain reaction-variable number of tandem repeat and polymorphism. The clinical data and tic symptoms was assessed with the clinical data schedule table and the Yale Global Tic Severity Scale ( YGTSS ). TS was diagnosed with the Diagnostic and Statistical Manual of Mental Disorders,the Forth Edition( DSM-Ⅳ )diagnostic criteria for Tourette syndrome. Results There was no significant differences in the frequencies of genotype for DAT1 gene 40 bp VNTR between normal controls ( 57 samples )and common TS children ( 52 samples ) and refractory TS children ( 63 samples ) (χ2 = 12. 638, P =0.125).The allele 440bp tended to be more in children with refractory TS(refractory TS:commmon TS:normal controls=8:1:0),but with no significat differences(χ2=11.352,P=0.053).Conclusions The DAT1 gene 40 bp VNTR 440 bp allele frequency seems to be higher in children with refractory TS,which suggests common TS and refractory TS have different genetic background. It should be verified by making larger samples in future study.     

Association of single nucleotide polymorphisms of brain-derived neurotrophic factor gene and multidrug resistance 1 gene to refractory epilepsy in Chinese Han children

BACKGROUND： There are two hypotheses for the underlying cause of refractory epilepsy： ＂target＂ and ＂transport＂. Studies have shown that brain-derived neurotrophic factor （BDNF） is over-expressed in refractory epilepsy. Multidrug resistance 1 （MDR1） gene encodes for P-glycoprotein, the primary ATP-binding cassette transporter in the human body. Some single nucleotide polymorphisms of the MDR1 gene have been associated with refractory epilepsy. OBJECTIVE： To investigate the association between BDNF gene C270T polymorphism and MDR1 T-129C polymorphism with refractory epilepsy in Chinese Han children through the use of polymerase chain reaction （PCR）-restriction fragment length polymorphism analysis. DESIGN, TIME AND SETTING： A case-control, genetic association study was performed at the Central Laboratory, Third Xiangya Hospital of Central South University from June 2005 to November 2007. PARTICIPANTS： A total of 84 cases of unrelated children with epilepsy, including 41 cases of refractory epilepsy and 43 cases of drug-responsive epilepsy, were enrolled. An additional 30 healthy, Chinese Han children, whose ages and gender matched the refractory epilepsy patients, were selected as normal controls. METHODS： Venous blood was collected and genomic DNA was extracted from the blood specimens. C270T polymorphism in BDNF gene and T-129C polymorphism in MDR1 gene were genotyped using PCR-restriction fragment length polymorphism analysis. Association analysis using the Ftest and Chi-square test was statistically performed between C270T polymorphism in BDNF gene and T-129C polymorphism in MDR1 gene and refractory epilepsy. MAIN OUTCOME MEASURES： The distribution of genotypes and allele frequencies of C270T polymorphism in BDNF gene and T-129C polymorphism in MDR1 gene. RESULTS： The distribution of CC, CT, and TT genotypes, as well as C and T allele frequencies, in the BDNF gene was not significantly different between the refractory epilepsy group, drug-responsive epilepsy group, or the normal control group （P 〉 0.05）. The distribution of TT genotype and T allele frequencies of the MDR1 gene was significantly different in the refractory epilepsy group compared with the drug-responsive epilepsy and normal control groups （P 〈 0.05）. Comparison of haplotype combinations demonstrated that there were no significant differences in combinations of TT＋CC, -FI-＋CT, TC＋CC, and TC＋CT among the three groups （P 〉 0.05）. CONCLUSION： C270T polymorphism of the BDNF gene was not associated with refractory epilepsy in Chinese Han children, but T-129C polymorphism in the MDR1 gene was associated with refractory epilepsy in Chinese Han children. The TT genotype and T allele frequencies could serve as susceptibility loci for refractory epilepsy. Interactions between C270T in BDNF gene and T-129C in MDR1 gene were not observed in refractory epilepsy in Chinese Han children.     

铁调节蛋白2基因多态性与阿尔茨海默病及血管性痴呆的相关分析

Objective To evaluate the association of 2616c/T polymorphism in iron regulatory protein 2(IRP2)gene with Alzheimer disease(AD)and Vascular dementia(VD).Methods In this study,281 patients with AD,60 with VD,and 285 normal aged were recruited.The 2616C/T polymorphism in IRP2 gene was analyzed by using polymerase chain reaction-restriction fragment length polymorphism.And the cognitive function was assessed with the Mini-Mental State Examination(MMSE).Results (1)No significant difieFences were demonstrated in IRP2 genotype or allele frequencies between AD patients and controls(χ2=2.46,P=0.292;χ2=2.17,P=0.141 respectively).However,when AD patients were stratified by disease severity.the frequency of T allele carriers in the moderate to severe AD patients was 78.0%,significantly higher than that in controls(69.8%;χ2=4.106,P＜0.05).Logistic regression analysis demonstrated that the age-,sex-and ApoE-adiusted OR of modcrate to severe AD patient with T allele was 1.62(95% CI=1.03-2.54).The frequency of T allele carriers or T allele in VD patients was higher than that of controls,but the difference was not statistically significant(P＞0.05).(2)The frequency of tit genotype or T allele in the moderate to severe AD patients was significantly higher than that in mild AD patients(25.8%vs.12.5%,χ2=5.477,P＜0.05;51.9%vs.40.3%,χ2=5.803,P＜0.05 respectively).(3)MMSE scores of the AD patients with TT genotype was significantly lower than ones with CC or CT genotype(P=0.028;P=0.014 respectively).Conclusion The 2616C/T polymorphism in the IRP2 gene is possibly associated with moderate to severe AD.but not associated with VD.And the TT genotype may be a risk factor for cognitive impairment of patients with AD in Chinese Han.     

铁调节蛋白2基因多态性与阿尔茨海默病及血管性痴呆的相关分析

Objective To evaluate the association of 2616c/T polymorphism in iron regulatory protein 2(IRP2)gene with Alzheimer disease(AD)and Vascular dementia(VD).Methods In this study,281 patients with AD,60 with VD,and 285 normal aged were recruited.The 2616C/T polymorphism in IRP2 gene was analyzed by using polymerase chain reaction-restriction fragment length polymorphism.And the cognitive function was assessed with the Mini-Mental State Examination(MMSE).Results (1)No significant difieFences were demonstrated in IRP2 genotype or allele frequencies between AD patients and controls(χ2=2.46,P=0.292;χ2=2.17,P=0.141 respectively).However,when AD patients were stratified by disease severity.the frequency of T allele carriers in the moderate to severe AD patients was 78.0%,significantly higher than that in controls(69.8%;χ2=4.106,P＜0.05).Logistic regression analysis demonstrated that the age-,sex-and ApoE-adiusted OR of modcrate to severe AD patient with T allele was 1.62(95% CI=1.03-2.54).The frequency of T allele carriers or T allele in VD patients was higher than that of controls,but the difference was not statistically significant(P＞0.05).(2)The frequency of tit genotype or T allele in the moderate to severe AD patients was significantly higher than that in mild AD patients(25.8%vs.12.5%,χ2=5.477,P＜0.05;51.9%vs.40.3%,χ2=5.803,P＜0.05 respectively).(3)MMSE scores of the AD patients with TT genotype was significantly lower than ones with CC or CT genotype(P=0.028;P=0.014 respectively).Conclusion The 2616C/T polymorphism in the IRP2 gene is possibly associated with moderate to severe AD.but not associated with VD.And the TT genotype may be a risk factor for cognitive impairment of patients with AD in Chinese Han.     

铁调节蛋白2基因多态性与阿尔茨海默病及血管性痴呆的相关分析

Objective To evaluate the association of 2616c/T polymorphism in iron regulatory protein 2(IRP2)gene with Alzheimer disease(AD)and Vascular dementia(VD).Methods In this study,281 patients with AD,60 with VD,and 285 normal aged were recruited.The 2616C/T polymorphism in IRP2 gene was analyzed by using polymerase chain reaction-restriction fragment length polymorphism.And the cognitive function was assessed with the Mini-Mental State Examination(MMSE).Results (1)No significant difieFences were demonstrated in IRP2 genotype or allele frequencies between AD patients and controls(χ2=2.46,P=0.292;χ2=2.17,P=0.141 respectively).However,when AD patients were stratified by disease severity.the frequency of T allele carriers in the moderate to severe AD patients was 78.0%,significantly higher than that in controls(69.8%;χ2=4.106,P＜0.05).Logistic regression analysis demonstrated that the age-,sex-and ApoE-adiusted OR of modcrate to severe AD patient with T allele was 1.62(95% CI=1.03-2.54).The frequency of T allele carriers or T allele in VD patients was higher than that of controls,but the difference was not statistically significant(P＞0.05).(2)The frequency of tit genotype or T allele in the moderate to severe AD patients was significantly higher than that in mild AD patients(25.8%vs.12.5%,χ2=5.477,P＜0.05;51.9%vs.40.3%,χ2=5.803,P＜0.05 respectively).(3)MMSE scores of the AD patients with TT genotype was significantly lower than ones with CC or CT genotype(P=0.028;P=0.014 respectively).Conclusion The 2616C/T polymorphism in the IRP2 gene is possibly associated with moderate to severe AD.but not associated with VD.And the TT genotype may be a risk factor for cognitive impairment of patients with AD in Chinese Han.     

铁调节蛋白2基因多态性与阿尔茨海默病及血管性痴呆的相关分析

Objective To evaluate the association of 2616c/T polymorphism in iron regulatory protein 2(IRP2)gene with Alzheimer disease(AD)and Vascular dementia(VD).Methods In this study,281 patients with AD,60 with VD,and 285 normal aged were recruited.The 2616C/T polymorphism in IRP2 gene was analyzed by using polymerase chain reaction-restriction fragment length polymorphism.And the cognitive function was assessed with the Mini-Mental State Examination(MMSE).Results (1)No significant difieFences were demonstrated in IRP2 genotype or allele frequencies between AD patients and controls(χ2=2.46,P=0.292;χ2=2.17,P=0.141 respectively).However,when AD patients were stratified by disease severity.the frequency of T allele carriers in the moderate to severe AD patients was 78.0%,significantly higher than that in controls(69.8%;χ2=4.106,P＜0.05).Logistic regression analysis demonstrated that the age-,sex-and ApoE-adiusted OR of modcrate to severe AD patient with T allele was 1.62(95% CI=1.03-2.54).The frequency of T allele carriers or T allele in VD patients was higher than that of controls,but the difference was not statistically significant(P＞0.05).(2)The frequency of tit genotype or T allele in the moderate to severe AD patients was significantly higher than that in mild AD patients(25.8%vs.12.5%,χ2=5.477,P＜0.05;51.9%vs.40.3%,χ2=5.803,P＜0.05 respectively).(3)MMSE scores of the AD patients with TT genotype was significantly lower than ones with CC or CT genotype(P=0.028;P=0.014 respectively).Conclusion The 2616C/T polymorphism in the IRP2 gene is possibly associated with moderate to severe AD.but not associated with VD.And the TT genotype may be a risk factor for cognitive impairment of patients with AD in Chinese Han.     

铁调节蛋白2基因多态性与阿尔茨海默病及血管性痴呆的相关分析

Objective To evaluate the association of 2616c/T polymorphism in iron regulatory protein 2(IRP2)gene with Alzheimer disease(AD)and Vascular dementia(VD).Methods In this study,281 patients with AD,60 with VD,and 285 normal aged were recruited.The 2616C/T polymorphism in IRP2 gene was analyzed by using polymerase chain reaction-restriction fragment length polymorphism.And the cognitive function was assessed with the Mini-Mental State Examination(MMSE).Results (1)No significant difieFences were demonstrated in IRP2 genotype or allele frequencies between AD patients and controls(χ2=2.46,P=0.292;χ2=2.17,P=0.141 respectively).However,when AD patients were stratified by disease severity.the frequency of T allele carriers in the moderate to severe AD patients was 78.0%,significantly higher than that in controls(69.8%;χ2=4.106,P＜0.05).Logistic regression analysis demonstrated that the age-,sex-and ApoE-adiusted OR of modcrate to severe AD patient with T allele was 1.62(95% CI=1.03-2.54).The frequency of T allele carriers or T allele in VD patients was higher than that of controls,but the difference was not statistically significant(P＞0.05).(2)The frequency of tit genotype or T allele in the moderate to severe AD patients was significantly higher than that in mild AD patients(25.8%vs.12.5%,χ2=5.477,P＜0.05;51.9%vs.40.3%,χ2=5.803,P＜0.05 respectively).(3)MMSE scores of the AD patients with TT genotype was significantly lower than ones with CC or CT genotype(P=0.028;P=0.014 respectively).Conclusion The 2616C/T polymorphism in the IRP2 gene is possibly associated with moderate to severe AD.but not associated with VD.And the TT genotype may be a risk factor for cognitive impairment of patients with AD in Chinese Han.     

铁调节蛋白2基因多态性与阿尔茨海默病及血管性痴呆的相关分析

Objective To evaluate the association of 2616c/T polymorphism in iron regulatory protein 2(IRP2)gene with Alzheimer disease(AD)and Vascular dementia(VD).Methods In this study,281 patients with AD,60 with VD,and 285 normal aged were recruited.The 2616C/T polymorphism in IRP2 gene was analyzed by using polymerase chain reaction-restriction fragment length polymorphism.And the cognitive function was assessed with the Mini-Mental State Examination(MMSE).Results (1)No significant difieFences were demonstrated in IRP2 genotype or allele frequencies between AD patients and controls(χ2=2.46,P=0.292;χ2=2.17,P=0.141 respectively).However,when AD patients were stratified by disease severity.the frequency of T allele carriers in the moderate to severe AD patients was 78.0%,significantly higher than that in controls(69.8%;χ2=4.106,P＜0.05).Logistic regression analysis demonstrated that the age-,sex-and ApoE-adiusted OR of modcrate to severe AD patient with T allele was 1.62(95% CI=1.03-2.54).The frequency of T allele carriers or T allele in VD patients was higher than that of controls,but the difference was not statistically significant(P＞0.05).(2)The frequency of tit genotype or T allele in the moderate to severe AD patients was significantly higher than that in mild AD patients(25.8%vs.12.5%,χ2=5.477,P＜0.05;51.9%vs.40.3%,χ2=5.803,P＜0.05 respectively).(3)MMSE scores of the AD patients with TT genotype was significantly lower than ones with CC or CT genotype(P=0.028;P=0.014 respectively).Conclusion The 2616C/T polymorphism in the IRP2 gene is possibly associated with moderate to severe AD.but not associated with VD.And the TT genotype may be a risk factor for cognitive impairment of patients with AD in Chinese Han.     

铁调节蛋白2基因多态性与阿尔茨海默病及血管性痴呆的相关分析

Objective To evaluate the association of 2616c/T polymorphism in iron regulatory protein 2(IRP2)gene with Alzheimer disease(AD)and Vascular dementia(VD).Methods In this study,281 patients with AD,60 with VD,and 285 normal aged were recruited.The 2616C/T polymorphism in IRP2 gene was analyzed by using polymerase chain reaction-restriction fragment length polymorphism.And the cognitive function was assessed with the Mini-Mental State Examination(MMSE).Results (1)No significant difieFences were demonstrated in IRP2 genotype or allele frequencies between AD patients and controls(χ2=2.46,P=0.292;χ2=2.17,P=0.141 respectively).However,when AD patients were stratified by disease severity.the frequency of T allele carriers in the moderate to severe AD patients was 78.0%,significantly higher than that in controls(69.8%;χ2=4.106,P＜0.05).Logistic regression analysis demonstrated that the age-,sex-and ApoE-adiusted OR of modcrate to severe AD patient with T allele was 1.62(95% CI=1.03-2.54).The frequency of T allele carriers or T allele in VD patients was higher than that of controls,but the difference was not statistically significant(P＞0.05).(2)The frequency of tit genotype or T allele in the moderate to severe AD patients was significantly higher than that in mild AD patients(25.8%vs.12.5%,χ2=5.477,P＜0.05;51.9%vs.40.3%,χ2=5.803,P＜0.05 respectively).(3)MMSE scores of the AD patients with TT genotype was significantly lower than ones with CC or CT genotype(P=0.028;P=0.014 respectively).Conclusion The 2616C/T polymorphism in the IRP2 gene is possibly associated with moderate to severe AD.but not associated with VD.And the TT genotype may be a risk factor for cognitive impairment of patients with AD in Chinese Han.     

铁调节蛋白2基因多态性与阿尔茨海默病及血管性痴呆的相关分析

Objective To evaluate the association of 2616c/T polymorphism in iron regulatory protein 2(IRP2)gene with Alzheimer disease(AD)and Vascular dementia(VD).Methods In this study,281 patients with AD,60 with VD,and 285 normal aged were recruited.The 2616C/T polymorphism in IRP2 gene was analyzed by using polymerase chain reaction-restriction fragment length polymorphism.And the cognitive function was assessed with the Mini-Mental State Examination(MMSE).Results (1)No significant difieFences were demonstrated in IRP2 genotype or allele frequencies between AD patients and controls(χ2=2.46,P=0.292;χ2=2.17,P=0.141 respectively).However,when AD patients were stratified by disease severity.the frequency of T allele carriers in the moderate to severe AD patients was 78.0%,significantly higher than that in controls(69.8%;χ2=4.106,P＜0.05).Logistic regression analysis demonstrated that the age-,sex-and ApoE-adiusted OR of modcrate to severe AD patient with T allele was 1.62(95% CI=1.03-2.54).The frequency of T allele carriers or T allele in VD patients was higher than that of controls,but the difference was not statistically significant(P＞0.05).(2)The frequency of tit genotype or T allele in the moderate to severe AD patients was significantly higher than that in mild AD patients(25.8%vs.12.5%,χ2=5.477,P＜0.05;51.9%vs.40.3%,χ2=5.803,P＜0.05 respectively).(3)MMSE scores of the AD patients with TT genotype was significantly lower than ones with CC or CT genotype(P=0.028;P=0.014 respectively).Conclusion The 2616C/T polymorphism in the IRP2 gene is possibly associated with moderate to severe AD.but not associated with VD.And the TT genotype may be a risk factor for cognitive impairment of patients with AD in Chinese Han.     

The homozygote 10-copy genotype of variable number tandem repeat dopamine transporter gene may confer protection against Parkinson's disease for male,but not to female patients

We investigated the role of variable number tandem repeat (VNTR) polymorphism of the dopamine transporter gene (DAT) in the pathogenesis of Parkinson's disease (PD) in Taiwanese. A case-control study was carried out to examine the association of the VNTR polymorphism within the DAT between 193 sporadic PD patients and 254 controls, matched by age and sex. Six alleles of VNTR polymorphism in the DAT, consisting of 6, 7, 8, 9, 10 and 11 copies of the 40-base-pair (bp) repeat sequence, were detected in the study. There were no differences of allele frequency (chi(2)=5.239, p=0.387) and genotype polymorphism of the DAT VNTR (chi(2)=11.873, p=0.157) in PD patients from the controls. Further analysis stratified by sex and age at onset did not show associations. However, PD patients carrying homozygote 10-copy genotype of the DAT VNTR polymorphism were 0.67 times fewer than controls (chi(2)=4.569, odds radio (OR)=0.67, 95% confidence interval (CI)=0.45-0.97, p=0.033). The reduced risk of the homozygosity with PD genotype was only in male PD patients (chi(2)=2.923, OR=0.48, 95% CI=0.25-0.93, p=0.026), but not in female PD patients (chi(2)=0.002, OR=1.02, 95% CI=0.49-2.11, p=0.966). In conclusion, the results of our study show that homozygote 10-copy genotype of the VNTR polymorphism within the DAT may confer a protective factor for male PD patients, but not for female PD patients.     

Effects of source of DNA on genotyping success rates and allele percentages in the Preschoolers with Attention-Deficit/Hyperactivity Disorder Treatment Study (PATS)

OBJECTIVE: In children diagnosed with attention-deficit/hyperactivity disorder (ADHD) and their parents, who were participants of the Preschool ADHD Treatment Study (PATS), we assessed the effect of source of DNA (from buccal or blood cells) on the genotyping success rate and allele percentages for the five polymorphisms in three candidate genes (DAT1, DRD4, and SNAP 25) investigated in the PATS pharmacogenetic study of response to stimulant medication. METHOD: At baseline assessment, 241 individuals (113 probands and 128 parents) consented to participate; 144 individuals (52 probands and 92 parents) provided blood samples from venipuncture, and 97 individuals (61 probands and 36 parents) provided buccal samples from cheek swab as specimens for isolation of DNA. Three types of polymorphisms-variable number of tandem repeat (VNTR) polymorphism, tandem duplication polymorphism (TDP), and single nucleotide polymorphism (SNP)-were evaluated, including the DRD4 gene 48-bp VNTR in exon III, the DAT1 gene 40-bp VNTR in 3'-untranslated region, the DRD4 gene TDP 120-bp duplication in the promoter region, the SNAP-25 gene TC-1069 SNP, and the SNAP-25 gene TG-1065 SNP. Standard procedures were used to genotype individuals for each of these five polymorphisms. RESULTS: Using the methods available in 2004, the genotyping success rate was on the average much greater for DNA from blood cells than buccal cells (e.g., 91% vs. 54% in probands). For some polymorphisms (DRD4-VNTR, DRD4-TDP, and SNAP25-TC SNP), allele proportion also varied by blood versus buccal source of DNA (e.g., 26.5% vs. 18.6% for the 7-repeat allele of the DRD4 gene). CONCLUSIONS: The much lower success rate for genotyping based on DNA from buccal than blood cells is likely due to the quality of DNA derived from these two sources. The observed source differences in allele proportion may be due to self-selection related to choice of how specimens were collected (from cheek swab or venipuncture), or to a selective detection of some alleles based on differences in DNA quality.     

多巴胺转运体基因与迟发性运动障碍的关联性

目的：探讨多巴胺转运体(DAT1)基因小卫星多态与迟发性运动障碍(TD)的关联性。方法：采用Amp—FLP技术，对99例精神分裂症伴TD患者和120名正常人的DAT1基因多态性进行检测，比较各组间等位基因和基因型频率分布的差异。结果：共观察到5种等位基因：320bp、360bp、440bp、480bp和520bp。经吻合度检验，TD组和正常对照组DAT1基因各基因型的分布均符合Hardy-Weinberg平衡法则。与正常对照组相比较，TD组中仅360bp等位基因频率显著减少(P＜0．05)。经关联性分析，DAT1基因该多态与TD不相关联。在TD组中，基因型频数及等位基因频数与病程、家族史、药物、剂量和异常不自主运动评定量表(AIMS)评分无显著性意义(P＞0．05)：结论：DAT1基因该位点多态可能与TD的发生无关。     

Dopamine transporter genotype predicts attentional asymmetry in healthy adults

A number of recent studies suggest that DNA variation in the dopamine transporter gene (DAT1) influences spatial attention asymmetry in clinical populations such as ADHD, but confirmation in non-clinical samples is required. Since non-spatial factors such as attentional load have been shown to influence spatial biases in clinical conditions, here we sought to determine whether any association between DAT1 genotype and spatial bias might be moderated by non-spatial attentional load. Healthy adults were asked to react to sudden onset peripheral targets while demand on non-spatial attention was manipulated via a central task. Participants were genotyped for a DAT1 variable number of tandem repeat (VNTR) polymorphism. The 10-repeat allele of this variant is a replicated susceptibility allele for ADHD and has been shown to associate with spatial bias. As expected, an overall leftward asymmetry/pseudoneglect was observed when the data were averaged across the entire sample. When data were stratified by DAT1 genotype, individuals lacking homozygosity for the 10-repeat DAT1 allele (non-10/10) showed a pronounced leftward bias that was significantly different from zero. In line with past reports from children with ADHD, this leftward bias was attenuated in individuals who were homozygous for the DAT1 10-repeat allele (10/10), suggestive of relatively weaker right hemisphere dominance for spatial attention. This effect of DAT1 genotype on spatial bias was not modulated by non-spatial attention load. These data confirm in healthy adult participants both the existence and the direction of the relationship previously reported between DAT1 genotype and spatial bias in children with ADHD. These data add to a growing body of evidence showing that spatial attentional asymmetry is a stable quantitative trait, with individual differences in this trait significantly predicted by common DNA variation in the DAT1 gene.     

Interacting effects of the dopamine transporter gene and psychosocial adversity on attention-deficit/hyperactivity disorder symptoms among 15-year-olds from a high-risk community sample

CONTEXT: Recent evidence suggests that gene x environment interactions could explain the inconsistent findings of association studies relating the dopamine transporter (DAT1) gene with attention-deficit/hyperactivity disorder (ADHD). OBJECTIVE: To examine whether psychosocial adversity moderated the effect of genetic variation in DAT1 on ADHD symptoms in adolescents from a high-risk community sample. DESIGN: Prospective cohort study. SETTING: Data were taken from the Mannheim Study of Children at Risk, an ongoing longitudinal study of the long-term outcomes of early risk factors followed up from birth on. PARTICIPANTS: Three hundred five adolescents (146 boys, 159 girls) participated in a follow-up assessment at age 15 years. MAIN OUTCOME MEASURES: Measures of ADHD symptoms according to DSM-IV were obtained using standardized structural interviews with adolescents and their parents. Psychosocial adversity was determined according to an "enriched" family adversity index as proposed by Rutter and Quinton. DNA was genotyped for the common DAT1 40-base pair (bp) variable number of tandem repeats (VNTR) polymorphism in the 3' untranslated region; 3 previously described single nucleotide polymorphisms in exon 15, intron 9, and exon 9; and a novel 30-bp VNTR polymorphism in intron 8. RESULTS: Adolescents homozygous for the 10-repeat allele of the 40-bp VNTR polymorphism who grew up in greater psychosocial adversity exhibited significantly more inattention and hyperactivity-impulsivity than adolescents with other genotypes or who lived in less adverse family conditions (significant interaction, P = .013-.017). This gene x environment interaction was also observed in individuals homozygous for the 6-repeat allele of the 30-bp VNTR polymorphism and the haplotype comprising both markers. CONCLUSIONS: These findings provide initial evidence that environmental risks as described by the Rutter Family Adversity Index moderate the impact of the DAT1 gene on ADHD symptoms, suggesting a DAT1 effect only in those individuals exposed to psychosocial adversity.     

Attention-deficit/hyperactivity disorder (ADHD) association with the DAT1 core promoter -67 T allele

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   

Dopamine transporter gene polymorphism, spect imaging, and levodopa response in patients with Parkinson disease

OBJECTIVES: To assess the potential association between dopamine transporter (DAT) genotype, single photon emission CT (SPECT) measures using [123I]-N-omega-fluoropropyl-2beta-carbomethoxy-3beta-(4-iodophenyl)nortropane ([123I]-FP-CIT) of striatal dopaminergic function, and oral levodopa response pattern in a cohort of patients with Parkinson disease. METHODS: Thirty-six patients at different disease stages enrolled in the study. Each patient was examined by [123I]-FP-CIT SPECT and a standardized oral levodopa test on 2 separate days in a randomized order within 3 weeks. The main outcome variables were the specific-to-nonspecific tracer uptake ratio in the contralateral putamen for SPECT analysis; latency, duration, and magnitude of the motor effect; and presence of dyskinesias for the levodopa test. The variable number of tandem repeat (VNTR) polymorphisms of the gene coding for DAT were detected for each patient by standard methods. RESULTS: Contralateral putamen [123I]-FP-CIT uptake ratios were similar in the patients carrying the 9-copy allele (n=20) of the DAT VNTR compared with 10-repeat homozygotes (n=16). No significant difference was found in levodopa main outcome variables and dyskinesia incidence between the two groups of patients stratified by DAT VNTR polymorphism. CONCLUSIONS: The study did not identify clinically relevant in vivo DAT neurochemical function phenotypes or levodopa response patterns associated with the DAT polymorphism.     

Association between the dopamine transporter gene and posttraumatic stress disorder

Posttraumatic stress disorder (PTSD) is a chronic anxiety disorder that follows exposure to extreme events. A large twin study of Vietnam veterans had demonstrated a significant genetic contribution to chronic PTSD upon exposure to combat.(1,2) The underlying genes, however, have not been described. Given previous findings of abnormal dopamine (DA) function in PTSD, and given the putative effect of dopamine neurotransmission in shaping the responses to stress in animals, this study examined the association of the dopamine transporter (DAT) SLC6A3 3' variable number tandem repeat (VNTR) polymorphism with PTSD. The study evaluated 102 chronic PTSD patients and 104 carefully-documented trauma survivors (TS) who did not develop PTSD. Significant excess of 9 repeat allele was observed among PTSD patients (43% vs 30.5% in TS controls; chi(2) = 6.3, df = 1, P = 0.012). An excess of 9 repeat homozygous genotype was also observed in PTSD (20.43% in PTSD vs 9.47% in TS controls; chi(2) = 6.11, df = 2, P < 0.047). These findings suggest that genetically determined changes in dopaminergic reactivity may contribute to the occurrence of PTSD among trauma survivors.     

Haplotype study of three polymorphisms at the dopamine transporter locus confirm linkage to attention-deficit/hyperactivity disorder.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is often treated using methylphenidate, a psychostimulant that inhibits the dopamine transporter. This led E.H. Cook and colleagues to consider the dopamine transporter locus (DAT1) as a primary candidate gene for ADHD. That group reported a significant association between ADHD and the 480-base pair (bp) allele of the variable number of tandem repeats (VNTR) polymorphism located in the 3' untranslated region of the DAT1 gene. This association was later replicated in additional studies. METHODS: The DAT1 gene has additional common polymorphisms in intron 9 and exon 9. We investigated the possibility of linkage of DAT1 and ADHD using the VNTR polymorphism and two additional common polymorphisms in 102 nuclear families with an ADHD proband. Using the transmission disequilibrium test, we examined the transmission of the alleles of each of these polymorphisms, as well as the haplotypes of the polymorphisms. RESULTS: We did not observe significant evidence for the biased transmission of the alleles of either the VNTR or the additional two polymorphisms when examined individually, although there was a trend for the biased transmission of the 480-bp allele of the VNTR. When we examined the haplotypes of the three polymorphisms we found significant evidence for biased transmission of one of the haplotypes containing the 480-bp VNTR allele. We also genotyped six additional DNA sequence variants of the DAT1 gene. However, these variants were not sufficiently polymorphic in our sample to be informative. Two of the DNA variants that result in an amino acid change, Ala559Val and Glu602Gly, were not observed in our sample. CONCLUSIONS: Our results support previous findings of an association between the DAT1 gene and ADHD.     

卒中后抑郁患者多巴胺代谢系统COMT和DAT基因多态性分析

目的 探讨多巴胺递质代谢相关蛋白儿茶酚氧位甲基转移酶(COMT)Val108/158Met、多巴胺转运体(DAT)40bp可变数目串联重复多态(VNTR)两位点基因多态性与卒中后抑郁(PSD)的关系.方法 选择南方医科大学珠江医院神经内科自2010年1月至2010年6月收治的PSD患者68例作为研究组,同期脑卒中后无抑郁患者91例作为对照组,利用聚合酶链式反应-限制性片段长度多态性(PCR-RFLP)技术分析患者COMT Val108/158Met、DAT 40 bp VNTR位点的基因多态性.结果 COMT基因扩增产物分野生型(G/G)、突变纯合型(A/A)、杂合型(A/G)3种基因型,DAT基因扩增产物分7/7、9/7、10/7、10/9、10/10、11/10、11/11倍重复7种基因型;2组患者COMT等位基因、基因型分布比较差异均有统计学意义(x2=5.703,P=0.017;x2=6.489,P=0.039).研究组男性患者与对照组男性患者之间比较,COMT等位基因、基因型的分布差异均无统计学意义(P＞0.05);研究组女性患者与对照组女性患者之间比较,COMT等位基因、基因型的分布差异均有统计学意义(x2=4.610,P=0.032;x2=6.547,P=0.024);研究组与对照组患者DAT等位基因和基因型的总体分布、杂合度比较差异均无统计学意义(P＞0.05).结论 COMT Val108/158Met基因多态性与PSD发生可能有相关性,而DAT40 bp VNTR基因多态性与PSD发生无明显相关性.

Abstract：

Objective To investigate the association of post-stroke depression (PSD) with gene polymorphisms of catechol-O-methyl transferase (COMT) Val1 08/158Met and dopamine transporter 40bp variable number of tandem repeats (VNTR) in dopamine metabolism system. Methods Sixty-eight patients with PSD and 91 patients only suffered from stroke, admitted to our hospital from January 2010to June 2010, were chosen; the gene polymorphisms ofCOMT Val108/158Met and DAT 40 bp VNTR were analyzed by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results The genotypes of COMT gene amplifications were wild type (G/G),homozygous mutant type (A/A) and heterozygous type (A/G); 7 repeated genotypes (7/7, 9/7, 10/7, 10/9,10/10, 11/10 and 11/11) were noted in the DA T gene amplifications; frequencies of COMT alleles and genotypes were significantly different between the 2 groups (x2=5.703, P=0.017;x2=6.489, P=0.039). The frequencies of COMT alleles and genotypes were significantly different between the 2 female groups (x2=4.610, P=0.032;x2=6.547, P=0.024), but no significant differences were found between the 2 male groups (P＞0.05). The frequencies and heterozygosity of DAT alleles and genotypes showed no obvious differences between the 2 groups (P＞0.05). Conclusion The gene polymorphism of COMT Val108/158Met may be associated with PSD, while that of DAT 40bp VNTR is not.