Replication of an association of a promoter polymorphism of the dopamine transporter gene and Attention Deficit Hyperactivity Disorder

Doyle, Christopher; Simpson, Jennifer; Park, Joanne; Scott, Sarah; Coghill, David; Hawi, Ziarih; Kirley, Aiveen; Gill, Michael; Kent, Lindsey

doi:10.1016/j.neulet.2009.06.084

Cited by 14 publications

(9 citation statements)

References 21 publications

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“…The 5′ flanking promoter polymorphisms in DAT1 may control transcriptional activity, thereby influencing DAT1 expression (Greenwood & Kelsoe 2003). Several studies have shown that the 5′ promoter polymorphisms of the DAT1 gene are associated with psychiatric disorders, such as attention‐deficit hyperactivity disorder (ADHD) and schizophrenia (Doyle et al 2009; Genro et al 2008; Huang et al 2010). Although previous studies have examined the association between the 3′ VNTR polymorphism of DAT1 and patients with HD (Gerra et al 2005; Hou & Li 2009), the potentially functional polymorphism in the 5′ promoter region and intron 8 VNTR of DAT1 has not, to our knowledge, been examined in the pathogenesis of HD (Greenwood & Kelsoe 2003; Hill et al 2009).…”

Section: Discussionmentioning

confidence: 99%

Neither single‐marker nor haplotype analyses support an association between the dopamine transporter gene and heroin dependence in Han Chinese

Yeh

Tao

et al. 2010

Genes Brain and Behavior

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Much evidence suggests that dysfunction of dopamine transporter-mediated dopamine transmission may be involved in the pathophysiology of substance abuse and dependence. The aim of this study was to examine whether the dopamine transporter gene (DAT1; SLC6A3) is associated with the development of heroin dependence (HD) and whether DAT1 influences personality traits in patients with HD. Polymorphisms of DAT1 were analyzed in a case-control study of 1046 Han Chinese (615 patients and 431 controls). All participants were screened using a Chinese version of the modified Schedule of Affective Disorder and SchizophreniaLifetime and all patients met the criteria for HD. Furthermore, a Chinese version of the Tridimensional Personality Questionnaire (TPQ) was used to assess personality traits in the patient group and examine the association between their personality traits and DAT1 polymorphisms. Of the patient group, 271 completed the TPQ. No statistically significant differences in allele or genotype frequencies of all investigated variants between HD patients and controls were observed. In haplotype analyses, four haplotype blocks of DAT1 were not associated with the development of HD. These DAT1 polymorphisms did not influence novelty seeking and harm avoidance scores in HD patients. This study suggests that the DAT1 gene may not contribute to the risk of HD and specific personality traits in HD among the Han Chinese population.

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Section: Discussionmentioning

confidence: 99%

Neither single‐marker nor haplotype analyses support an association between the dopamine transporter gene and heroin dependence in Han Chinese

Yeh

Tao

et al. 2010

Genes Brain and Behavior

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“…Hill et al [117] indicated that the intron 8 VNTR is a functional variant with an ADHD susceptibility allele having reduced activity (see also [93,118,119]). Joober et al [120] presented findings that support a role for the DAT gene 3’-UTR VNTR polymorphism in modulating the response of some behavioral dimensions to methylphenidate in children with ADHD.…”

Section: Parent-of-origin Effectsmentioning

confidence: 99%

Epigenetics in Developmental Disorder: ADHD and Endophenotypes

Archer

Oscar‐Berman²,

Blum³

2011

J Genet Syndr Gene Ther

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Heterogeneity in attention-deficit/hyperactivity disorder (ADHD), with complex interactive operations of genetic and environmental factors, is expressed in a variety of disorder manifestations: severity, co-morbidities of symptoms, and the effects of genes on phenotypes. Neurodevelopmental influences of genomic imprinting have set the stage for the structuralphysiological variations that modulate the cognitive, affective, and pathophysiological domains of ADHD. The relative contributions of genetic and environmental factors provide rapidly proliferating insights into the developmental trajectory of the condition, both structurally and functionally. Parent-of-origin effects seem to support the notion that genetic risks for disease process debut often interact with the social environment, i.e., the parental environment in infants and young children. The notion of endophenotypes, markers of an underlying liability to the disorder, may facilitate detection of genetic risks relative to a complex clinical disorder. Simple genetic association has proven insufficient to explain the spectrum of ADHD. At a primary level of analysis, the consideration of epigenetic regulation of brain signalling mechanisms, dopamine, serotonin, and noradrenaline is examined. Neurotrophic factors that participate in the neurogenesis, survival, and functional maintenance of brain systems, are involved in neuroplasticity alterations underlying brain disorders, and are implicated in the genetic predisposition to ADHD, but not obviously, nor in a simple or straightforward fashion. In the context of intervention, genetic linkage studies of ADHD pharmacological intervention have demonstrated that associations have fitted the "drug response phenotype," rather than the disorder diagnosis. Despite conflicting evidence for the existence, or not, of genetic associations between disorder diagnosis and genes regulating the structure and function of neurotransmitters and brainderived neurotrophic factor (BDNF), associations between symptoms-profiles endophenotypes and single nucleotide polymorphisms appear reassuring.

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“…A well replicated association has been found between the 10-repeat allele and attention deficit hyperactivity disorder (ADHD) (for review see: Gizer et al, 2009;Sharp et al, 2009;Vandenbergh et al, 2000), However, other studies, including a metaanalysis of family-based association studies yielded negative results (Holmes et al, 2000;Purper-Ouakil et al, 2005). The DAT 5′ VNTR polymorphism has also been found to be associated with ADHD (Doyle et al, 2009;Genro et al, 2008).…”

Section: Dopamine Transporter Polymorphismsmentioning

confidence: 99%

Imaging the effects of genetic polymorphisms on radioligand binding in the living human brain: A review on genetic neuroreceptor imaging of monoaminergic systems in psychiatry

Willeit

Praschak-Rieder

2010

NeuroImage

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Replication of an association of a promoter polymorphism of the dopamine transporter gene and Attention Deficit Hyperactivity Disorder

Cited by 14 publications

References 21 publications

Neither single‐marker nor haplotype analyses support an association between the dopamine transporter gene and heroin dependence in Han Chinese

Neither single‐marker nor haplotype analyses support an association between the dopamine transporter gene and heroin dependence in Han Chinese

Epigenetics in Developmental Disorder: ADHD and Endophenotypes

Imaging the effects of genetic polymorphisms on radioligand binding in the living human brain: A review on genetic neuroreceptor imaging of monoaminergic systems in psychiatry

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