A human dopamine transporter cDNA predicts reduced glycosylation, displays a novel repetitive element and provides racially-dimorphic TaqI RFLPs

Vandenbergh, David J.; Persico, Antonio M.; Uhl, George R.

doi:10.1016/0169-328x(92)90165-8

Cited by 187 publications

(95 citation statements)

References 20 publications

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“…88 A 40-bp VNTR polymorphism (3-13 repeats) has been identified in the 3 0 -untranslated region (UTR) of SCL6A3 encoding DAT1. 89,90 The SCL6A3-9-and 10-repeat alleles occur most frequently in humans, 91,92 but their functional impacts are unclear. 88,93 The SLC6A3-9 allele has been associated with a lower risk of current smoking and starting smoking before age 16 years, longer periods of abstinence during previous quit attempts and increased quitting.…”

Section: Dopamine Transportermentioning

confidence: 99%

Overview of the pharmacogenomics of cigarette smoking

Tyndale

2007

Pharmacogenomics J

102

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Cigarette smoking increases the risk of numerous health problems, including cancer, cardiovascular and pulmonary disorders, making smoking the leading cause of preventable death in the world. Nicotine is primarily responsible for the highly addictive properties of cigarettes. Although the majority of smokers express a desire to quit, few are successful in doing so. Twin and family studies have indicated substantial genetic contributions to smoking behaviors. One major research focus has been to elucidate the specific genes involved; this has been accomplished primarily through genome-wide linkage analyses and candidate gene association studies. Much attention has focused on genes involved in the neurotransmitter pathways for the brain reward system and genes altering nicotine metabolism. This paper reviews the current state of knowledge for genetic factors implicated in smoking behaviors, and examines how genetic variations may affect therapeutic outcomes for drugs used to assist smoking cessation.

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Section: Dopamine Transportermentioning

confidence: 99%

Overview of the pharmacogenomics of cigarette smoking

Tyndale

2007

Pharmacogenomics J

102

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“…DAT regulates the reuptake of dopamine from the extracellular space, thereby terminating its synaptic action. A genetic polymorphism identified as a potential risk factor for ADHD is a 40-bp variable number of tandem repeats (VNTR) polymorphism within the 3 0 untranslated region (UTR) of SLC6A3 (Vandenbergh et al, 1992). It has two common alleles designated as nine-repeat and 10-repeat, which have been suggested to influence SLC6A3 expression and, thereby, dopamine regulation (Mill et al, 2002;vanNess et al, 2005;Fuke et al, 2001;Miller and Madras, 2002;Greenwood andKelsoe, 2003 Michelhaugh et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

Dopamine Transporter (SLC6A3) Genotype Impacts Neurophysiological Correlates of Cognitive Response Control in an Adult Sample of Patients with ADHD

Dresler

Ehlis

Renner

et al. 2010

Neuropsychopharmacol

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Studies provide ample evidence for a dysfunction in dopaminergic neurotransmission in Attention-Deficit/Hyperactivity Disorder (ADHD). In that respect, a common variable number of tandem repeats (VNTR) polymorphism in the 3 0 untranslated region (UTR) of the dopamine transporter gene (SLC6A3) has been repeatedly associated with the disorder. Here, we examined the influence of the common 9-and 10-repeat alleles of SLC6A3 on prefrontal brain functioning and cognitive response control in a large sample of adult ADHD patients (n ¼ 161) and healthy controls (n ¼ 109). To this end, we inspected a neurophysiological marker of cognitive response control (NoGo anteriorization, NGA) elicited by means of a Go-NoGo task (continuous performance test, CPT). Within the group of ADHD patients, nine-repeat allele carriers showed significantly reduced NGA, whereas no influence of SLC6A3 genotype was observed in the control group. In contrast to previous association studies of children, the nine-repeatFnot the 10-repeatFallele was associated with functional impairments in our sample of adult ADHD patients. Our findings confirm a significant effect of the SLC6A3 genotype on the neurophysiological correlates of cognitive response control in ADHD, and indicate that still to-be-identified age-related factors are important variables modulating the effect of genetic factors on endophenotypes.

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“…10 Reuptake of dopamine into presynaptic neurons by means of DAT1 is believed to be the primary mechanism for termination of dopaminergic neurotransmission. Studies using single photon emission computed tomography revealed that the highest concentrations of DAT1 are found in the basal ganglia, and striatal density was shown to be markedly lower in non-violent alcoholics.…”

Section: Introductionmentioning

confidence: 99%

Identification of a novel polymorphism of the human dopamine transporter (DAT1) gene and the significant association with alcoholism

et al. 1999

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Human dopamine transporter gene (DAT1) has a variable number of tandem repeats (VNTR) in its 3Ј-untranslated region (UTR).The association between the VNTR polymorphism and neuropsychiatric disorders has been studied, but their relationship is still unclear. Here we identified a novel polymorphism in the 3Ј-UTR of the DAT1 gene, G2319A, and a significant association between the polymorphism and alcoholism was observed in both genotypic and allelic frequencies (P = 0.040 and 0.019, extended Fisher's exact test, respectively). There was a significant gene dose effect on the risk for alcoholism associated with the 2319-A allele ( 2 = 6.16, df = 2, P = 0.046, linearity tendency test: Cochranq-Armitage analysis). Moreover, in the haplotype analysis with G2319A-and VNTR-polymorphisms, a positive gene dose efffect on the risk with the A10 allele (P = 0.044, linearity tendency test) and a negative gene dose effect with the G10 allele (P = 0.010, linearity tendency test) for alcoholism were significantly detected. Odds ratio for alcoholism with the A10 and G10 alleles were 1.76 (1.12-2.76) and 0.53 (0.32-0.79), respectively. These results indicate that the DAT1 gene may confer vulnerability to alcoholism.

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A human dopamine transporter cDNA predicts reduced glycosylation, displays a novel repetitive element and provides racially-dimorphic TaqI RFLPs

Cited by 187 publications

References 20 publications

Overview of the pharmacogenomics of cigarette smoking

Overview of the pharmacogenomics of cigarette smoking

Dopamine Transporter (SLC6A3) Genotype Impacts Neurophysiological Correlates of Cognitive Response Control in an Adult Sample of Patients with ADHD

Identification of a novel polymorphism of the human dopamine transporter (DAT1) gene and the significant association with alcoholism

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