DAT1 gene polymorphism in alcoholism: a family-based association study

Franke, Petra; Schwab, Sibylle G.; Knapp, Michael; Gänsicke, Michael; Delmo, Cynthia D.; Zill, Peter; Trixler, M.; Lichtermann, Dirk; Hallmayer, Joachim; Wildenauer, Dieter B.; Maier, Wolfgang

doi:10.1016/s0006-3223(98)00135-8

Cited by 48 publications

(27 citation statements)

References 12 publications

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“…Moreover, genotype frequencies did not significantly differ from the HardyWeinberg equilibrium either in the overall sample or in alcoholics and controls separately (Table 1). This absence of association between DAT genotype and alcoholism, per se, is consistent with previously published results (Parsian and Zhang 1997;Franke et al 1999). DAT availability also did not differ significantly between alcoholics and controls in either putamen (t ϭ 0.80, df ϭ 23, p ϭ .43) or caudate (t ϭ 1.15, df ϭ 23, p ϭ .26), consistent with our earlier report on exclusively male subjects (Heinz et al 1998).…”

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confidence: 93%

Genotype Influences In Vivo Dopamine Transporter Availability in Human Striatum

Heinz

2000

Neuropsychopharmacology

510

381

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In vivo availability of striatal dopamine transporter (DAT) protein has been reported to be reduced among alcoholics, and allelic variation of the DAT gene (SLC6A3) has been associated with severity of alcohol withdrawal. We examined the VNTR polymorphism of the 3 Ј untranslated region of SLC6A3 and DAT protein availability inDysfunction of central dopaminergic neurotransmission has been associated with the development and maintenance of excessive alcohol consumption (Cloninger 1987;Wise 1988;Robinson and Berridge 1993). In animal experiments, ethanol consumption induces dopamine (DA) release in the mesolimbic reward system and may thus reinforce alcohol intake (Mereu et al. 1984;Imperato and Di Chiara 1986). Chronic alcohol consumption has been associated with increased dopamine turnover rate in humans (Heinz et al. 1996a) and with decreased dopamine receptors and transporters in non-human primates (Mash et al. 1996).Among alcoholics, a reduction in dopamine transporter (DAT) availability has been observed only in late-onset (type I) alcoholics (Tiihonen et al. 1995). The reasons for the reported selective reduction of dopamine transporters in late-onset alcoholics are unclear. They may include genetic and non-genetic factors such as the neurobiological correlates of personality or the effects of chronic alcohol intake (Cloninger 1995; Goldman 1995a,b). Vandenbergh et al. (1992) have identified a polymorphism of the 3 Ј untranslated region of the DAT gene (SLC6A3) that has been associated with se- (Sander et al. 1997;Schmidt et al. 1998). The same polymorphism has also been associated with attention deficit hyperactivity disorder (ADHD) in children (Cook et al. 1995) and with the severity of ADHD symptoms (Waldman et al. 1998). Furthermore, Gelernter et al. (1994) observed a significant association of this polymorphism with paranoia induced by cocaine, a potent DAT blocker, and Sabol et al. (1999) recently reported an association of this polymorphism with ease of smoking cessation. Because each of these clinical associations could conceivably be explained by genetically determined variations in synaptic dopamine, we examined the relationship of this polymorphism to variations in the availability of the DAT protein. The variable number of tandem repeat (VNTR) polymorphism in the 3 Ј region of SLC6A3 was genotyped and the availability of striatal DAT protein was measured in abstinent alcoholics and control subjects. Single photon emission computed tomography (SPECT) with the radioligand [I-123]-2 ␤ -carbomethoxy-3 ␤ -(4-iodophenyl)tropane ([I-123] ␤ -CIT) was used to determine the effective binding potential, a quantitative measure of DAT availability (Laruelle et al. 1994). METHODS SubjectsFourteen abstinent alcoholics (three females and 11 males) and eleven age-matched control subjects (four females and seven males) participated in this study. All subjects provided written informed consent for this study under protocols approved by the Institutional Review Boards of the Intramural Research Programs of the Nat...

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confidence: 93%

Genotype Influences In Vivo Dopamine Transporter Availability in Human Striatum

Heinz

2000

Neuropsychopharmacology

510

381

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“…A growing number of previous studies have reported an association between putative functionally relevant dopamine transporter polymorphisms and withdrawal seizures or delirium tremens in alcoholdependent subjects, [31][32][33][34] while some of these positive findings are not unanimously confirmed by other research groups using a more specific but less powerful family-based association approach. 35 In mice, an association between quantitative trait loci in proximity to genes that directly or indirectly affect gammaaminobutyric acid (GABA)-A receptor-mediated transmission and withdrawal intensity have been reported. 36 Reduced coupling between the GABA recognition site on the GABA-A receptor and the chloride channel has been noted.…”

Section: Discussionmentioning

confidence: 99%

Ionotropic glutamate receptor gene GRIK3 SER310ALA functional polymorphism is related to delirium tremens in alcoholics

et al. 2005

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“…Less consistently, alleles with the 9-repeat length have been associated with cocaine-induced paranoia and alcohol or nicotine addictions. [35][36][37][38][39][40][41][42] Emergent from these findings is whether the number Figure 1 Schematic representation of the human dopamine transporter gene. Shaded exons in the DNA form the coding region, white exons contribute to the 5Ј and 3Ј non-coding regions.…”

Section: Introductionmentioning

confidence: 99%