Family based association study of pediatric bipolar disorder and the dopamine transporter gene (<i>SLC6A3</i>)

Mick, Eric; Kim, Jang Woo; Biederman, Joseph; Wozniak, Janet; Wilens, Timothy E.; Spencer, Thomas; Smoller, Jordan W.; Faraone, Stephen V.

doi:10.1002/ajmg.b.30745

Cited by 47 publications

(41 citation statements)

References 44 publications

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“…The impact of the rs40184 polymorphism on the susceptibility of MDD is of immense interest since it has been recently shown to be associated with specific neuropsychiatric and neurological disorders (Haeffel et al, 2008;Zhou et al, 2008;Mick et al, 2008;Todt et al, 2009). Although the molecular connection between this SNP and cellular DAT1 level has not been demonstrated, many reports in the literature link polymorphisms of unknown function to certain psychiatric diseases (Cook Jr. et al, 1995).…”

Section: Discussionmentioning

confidence: 99%

“…This particular SNP has also been found to play a genetic role in certain neuropsychiatric and neurological illnesses such as attention deficit hyperactivity disorder (Zhou et al, 2008), bipolar disorder (Mick et al, 2008) and migraine with aura (Todt et al, 2009). With regard to the genotyping technologies used in the research findings addressed above, the rs40184 polymorphism was genotyped on one of the high-throughput platforms, particularly Sequenom, Taqman and Illumina.…”

Section: Introductionmentioning

confidence: 99%

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Association of C/T polymorphism in intron 14 of the dopamine transporter gene (rs40184) with major depression in a northeastern Thai population

Pattarachotanant¹,

Sritharathikhun²,

Suttirat³

et al. 2010

Genet. Mol. Res.

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ABSTRACT. Several lines of evidence suggest that the dopaminergic system is involved in the pathophysiology of major depressive disorder (MDD). Since the dopamine transporter (DAT1, also known as SLC6A3), mediates the active reuptake of dopamine from the synapses and thereby plays a vital role in the regulation of dopaminergic neurotransmission, we looked for a possible association between the C/T single nucleotide polymorphism in intron 14 of the DAT1 gene (also referred to as rs40184) and MDD in a northeastern Thai population. One hundred and seventyeight patients with MDD and 205 unrelated healthy controls were included in our study. Genotyping was performed using our newly established polymerase chain reaction-restriction fragment length polymorphism technique. We found no significant differences in genotype distributions, allele frequencies and allele carrier frequencies when comparing the two groups. Although not significant, we observed more carriers of the C allele (CC+CT genotypes) in healthy controls than in patients with MDD (χ 2  = 3.20, degrees of freedom = 1, P = 0.073, odds ratio = 0.53 [95% confidence interval = 0.28-1.01]). We also detected significant differences in the allele frequencies of rs40184 between healthy subjects of Asian ancestry and those of both Caucasian and African ancestry. We concluded that there is a tendency towards an association between the homozygous TT genotype of the rs40184 single nucleotide polymorphism and an increased risk for MDD in this northeastern Thai population. Possibly, with more samples, this tendency will be confirmed.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Association of C/T polymorphism in intron 14 of the dopamine transporter gene (rs40184) with major depression in a northeastern Thai population

Pattarachotanant¹,

Sritharathikhun²,

Suttirat³

et al. 2010

Genet. Mol. Res.

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“…A lower cerebral basal dopamine concentration in patients with the mutant genotype of the SLC6A3 gene could diminish the risk for delirium. The other SNP of interest in the SLC6A3 gene rs40184 is associated with bipolar disorder and conduct disorder in children, which shows some overlapping symptoms with delirium [Mick et al, 2008].…”

Section: Discussionmentioning

confidence: 99%

Genetic polymorphisms in the DRD2, DRD3, and SLC6A3 gene in elderly patients with delirium

Munster

Yazdanpanah

Tanck

et al. 2009

American J of Med Genetics Pt B

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Dopamine excess appears to be critical in the final common pathway of delirium. The aim of this study was to investigate whether genetic polymorphisms in three dopamine-related genes (the dopamine receptor 2 (DRD2), dopamine receptor 3 (DRD3), and the dopamine transporter (SLC6A3) gene) were associated with delirium. Patients aged 65 years and older acutely admitted to the medical department or to the surgical department following hip fracture were included. Delirium was diagnosed by the Confusion Assessment Method. Sixteen single nucleotide polymorphisms (SNPs) and one variable number of tandem repeats in the SLC6A3 gene, nine SNPs in the DRD2 gene, and six SNPs in the DRD3 gene were genotyped. Fifty percent of the 115 surgical patients and 34% of the 605 medical patients experienced delirium. Delirious patients were older and had more frequently pre-existing functional and cognitive impairment (P < 0.001). After correction for multiple testing, one SNP in the SLC6A3 gene (rs393795) was associated with reduced risk of delirium (P = 0.032). Adjusted for age, cognitive impairment, and functional impairment, three SNPs in the DRD2 gene and seven SNPs in the SLC6A3 gene were associated with delirium; none of these associations was significant after correction for multiple testing. Variations in the SLC6A3 gene and possibly the DRD2 gene were associated with delirium. Although validation of these results is needed our results support a role for the dopamine transporter and dopamine receptor 2 in the pathogenesis of delirium.

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“…Given the central role of dopamine in regulation of mood and behaviour, it's not surprising that several studies have evidenced that DAT1 is the major candidate gene in the pathogenesis of externalizing problems in childhood. In particular, genetic association studies have linked DAT1 gene to ADHD (Fernandez-Jaen et al 2015;Sokolova et al 2015;Thissen et al 2015, Giana et al, 2015, conduct disorder (Lahey et al, 2011), and pediatric bipolar disorder (Mick et al, 2008). Regarding genetic variants of DAT1, the pioneering study of Cook et al, (1995) have reported a significant association between ADHD and the 10-repeat allele of DAT1.…”

Section: Dopamine Transportermentioning

confidence: 99%

Dopamine Transporter And Transmission Of Psychopathological Risk. A Review Of Gene-Environment Interplay

Marzilli¹,

Ballarotto²,

Cimino³

et al. 2017

European Proceedings of Social and Behavioural Sciences

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Research underlines that intergenerational transmission of psychopathological risk results from a complex interplay of genetic and environmental risk factors which predispose child to develop emotionalbehavioral problems. Mechanisms of transmission are poorly understood, but few studies have focused on the role played by dopamine transporter (DAT) gene. This review aims to examine mediating mechanism of DAT genotype-environmental interaction (GxE), DAT genotype-environmental correlation (rGE), and methylation status involved in transmission of psychopathological risk. The review of literature was made through researches in university libraries on paper material, and telematics systems research. Studies have evidenced that DAT is implicated in intergenerational transmission of psychopathological risk. Results are mixed regarding its genetic variants, but mechanisms through which this gene can affect both quality of parenting and child development are partially established. Only few studies have examined methylation mechanisms that can be implicated. Findings suggest to involve an improved focus on DAT genotypes, methylation status associated, and their relationship with environment to better understanding child's vulnerability and resilience following exposure to contextual risk factors associated with parental psychopathological symptoms.

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Family based association study of pediatric bipolar disorder and the dopamine transporter gene (SLC6A3)

Cited by 47 publications

References 44 publications

Association of C/T polymorphism in intron 14 of the dopamine transporter gene (rs40184) with major depression in a northeastern Thai population

Association of C/T polymorphism in intron 14 of the dopamine transporter gene (rs40184) with major depression in a northeastern Thai population

Genetic polymorphisms in the DRD2, DRD3, and SLC6A3 gene in elderly patients with delirium

Dopamine Transporter And Transmission Of Psychopathological Risk. A Review Of Gene-Environment Interplay

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