Association of the DRD4 Exon III Polymorphism With Smoking in Fifteen-Year-Olds: A Mediating Role for Novelty Seeking?

Laucht, Manfred; Becker, Katja; El‐Faddagh, Mahha; Hohm, Erika; Schmidt, Martin H.

doi:10.1097/01.chi.0000155980.01792.7f

Cited by 85 publications

(74 citation statements)

References 26 publications

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“…Our results concur with some [17,20,23,34,38], but disagree with other [6,11,18,24,29] results. Although there are findings showing an association of long DRD4 gene allele and smoking only in men [17], the majority of previous studies did not find sex differences in the distribution of long and short alleles [6,24,34] and our data are in line with these findings. DRD4 VNTR gene variants were in HWE in the group of smokers, while in non-smoker group DRD4 VNTR deviated from HWE.…”

Section: Discussionsupporting

confidence: 68%

“…Hypothesis about the association of long DRD4 gene allele (7 and more repeats) with greater urge for smoking is confirmed on 68 smokers from USA [11]. The study carried out on 384 German adolescents showed an association of long DRD4 gene allele (7 and more repeats) with smoking for males but not for females [17]. The same research group confirmed an association of long DRD4 gene allele, long term smoking and lower rates of smoking cessation.…”

Section: Discussionmentioning

confidence: 74%

“…The results showing the association between nicotine addiction and DRD4 VNTR are conflicting. No association between DRD4 VNTR polymorphism and smoking [17,20,23,34,38], or significant association between DRD4 VNTR and nicotine dependence [6,11,18,24,29] was previously reported.…”

Section: Introductionmentioning

confidence: 92%

See 2 more Smart Citations

Lack of association between dopamine receptor D4 variable numbers of tandem repeats gene polymorphism and smoking

Babić

Nedić

Mück‐Šeler

et al. 2012

Neuroscience Letters

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Section: Discussionsupporting

confidence: 68%

Section: Discussionmentioning

confidence: 74%

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Lack of association between dopamine receptor D4 variable numbers of tandem repeats gene polymorphism and smoking

Babić

Nedić

Mück‐Šeler

et al. 2012

Neuroscience Letters

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“…79 Individuals with the L-allele also experienced greater craving, more arousal, less positive affect and more attention to smoking cues than individuals with the S-allele. 80 In adolescents, the L-allele (seven-repeat) increased the risk of smoking and novelty seeking in males; 81 however, another study failed to replicate these findings. 82 There is modest evidence for a role of DRD1, DRD3 or DRD5 in smoking behaviors.…”

Section: Mk Ho and Rf Tyndale 86mentioning

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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“…Noteworthy, there is substantial genetic influence in these sensation-seeking traits: for instance, the dopamine (DA) D4 receptor is the prototypic polymorphic gene subserving a background for novelty seeking (Ebstein et al, 1996), drug abuse (Laucht et al, 2005) and vulnerability to attention-deficit hyperactivity disorder (ADHD) and PG (Comings et al, 1999).…”

mentioning

confidence: 99%

Increased impulsive behavior and risk proneness following lentivirus-mediated dopamine transporter over-expression in rats' nucleus accumbens

et al. 2009

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Abstract-Multiple theories have been proposed for sensation seeking and vulnerability to impulse-control disorders [Zuckerman M, Kuhlman DM (2000) Personality and risk-taking: Common biosocial factors. J Pers 68:999 -1029], and many of these rely on a dopamine system deficit. Available animal models reproduce only some behavioral symptoms and seem devoid of construct validity. We used lentivirus tools for over-expressing or silencing the dopamine transporter (DAT) and we evaluated the resulting behavioral profiles in terms of motivation and self-control. Wistar adult rats received stereotaxic inoculation of a lentivirus that allowed localized intra-accumbens delivery of a DAT gene enhancer/ silencer, or the green fluorescent protein, GFP. These animals were studied for intolerance to delay, risk proneness and novelty seeking. As expected, controls shifted their demanding from a large reward toward a small one when the delivery of the former was increasingly delayed (or uncertain). Interestingly, in the absence of general locomotor effects, DAT over-expressing rats showed increased impulsivity (i.e. a more marked shift of demanding from the large/ delayed toward the small/soon reward), and increased risk proneness (i.e. a less marked shift from the large/uncertain toward the small/sure reward), compared with controls. Rats with enhanced or silenced DAT expression did not show any significant preference for a novel environment. In summary, consistent with literature on comorbidity between attentiondeficit/hyperactivity disorder and pathological gambling, we demonstrate that DAT over-expression in rats' nucleus accumbens leads to impulsive and risk prone phenotype. Thus, a reduced dopaminergic tone following altered accumbal DAT function may subserve a sensation-seeker phenotype and the vulnerability to impulse-control disorders.

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Association of the DRD4 Exon III Polymorphism With Smoking in Fifteen-Year-Olds: A Mediating Role for Novelty Seeking?

Cited by 85 publications

References 26 publications

Lack of association between dopamine receptor D4 variable numbers of tandem repeats gene polymorphism and smoking

Lack of association between dopamine receptor D4 variable numbers of tandem repeats gene polymorphism and smoking

Overview of the pharmacogenomics of cigarette smoking

Increased impulsive behavior and risk proneness following lentivirus-mediated dopamine transporter over-expression in rats' nucleus accumbens

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