Association between the DRD2 A1 allele and opium addiction in the Iranian population

Najafabadi, Maria Shahmoradgoli; Ohadi, Mina; Joghataie, Mohammad Taghi; Valaie, F; Riazalhosseini, Yasser; Mostafavi, Hamid; Mohammadbeigi, Fariba; Najmabadi, Hossein

doi:10.1002/ajmg.b.30117

Cited by 32 publications

(13 citation statements)

References 24 publications

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“…ANKK1/DRD2 SNPs were associated with heroin or cocaine addiction/abuse in different populations (Al-Eitan et al, 2012; Clarke et al, 2014; Jacobs et al, 2013a; Lawford et al, 2000; Li et al, 2006; Nelson et al, 2013; Perez de los Cobos et al, 2007; Shahmoradgoli Najafabadi et al, 2005; Vereczkei et al, 2013; Xu et al, 2004). In addition, a DRD1 SNPs were associated with heroin abuse (Jacobs et al, 2013a,b), a DBH SNP was associated with progressive OD in Han Chinese (Xie et al, 2013), and CSNK1E SNPs were associated with OD in subjects with European descent (Levran et al, 2008) and Han Chinese (Wang et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

Overlapping Dopaminergic Pathway Genetic Susceptibility to Heroin and Cocaine Addictions in African Americans

Levran

Randesi

Rosa

et al. 2015

Annals of Human Genetics

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Summary Drugs of abuse activate the mesolimbic dopaminergic pathway. Genetic variations in the dopaminergic system may contribute to vulnerability to drug addiction. Several processes are shared between cocaine and heroin addictions but some neurobiological mechanisms and environmental influence may be specific. This study examined the association of 98 single nucleotide polymorphisms (SNPs) in 13 dopamine pathway-related genes with heroin and/or cocaine addiction in a sample of 801 African Americans (315 subjects with heroin addiction (OD), with or without cocaine (CD) or alcohol addiction (AD), 279 subjects with CD, with or without AD, and 207 controls). Single-marker analyses provided nominally significant evidence for associations of 24 SNPs in DRD1, ANKK1/DRD2, DRD3, DRD5, DBH, DDC, COMT and CSNK1E with OD and/or CD. A DRD2 7-SNPs haplotype block that includes SNPs rs1075650 and rs2283265, which were shown to alter D2S/D2L splicing, was indicated in both addictions. The Met allele of the COMT Val158Met functional variant was associated with protection from OD. None of the signals remained significant after correction for multiple testing. The study results are in accordance with the results of several previous studies, including our report of association of DRD1 SNP rs5326 with OD in a smaller sample from this cohort. The findings suggest the presence of an overlap in the genetic liability for heroin and cocaine addictions, as well as shared and distinct liability for OD in subjects of African and European descent.

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Section: Introductionmentioning

confidence: 99%

Overlapping Dopaminergic Pathway Genetic Susceptibility to Heroin and Cocaine Addictions in African Americans

Levran

Randesi

Rosa

et al. 2015

Annals of Human Genetics

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“…Neuroanatomically, both disorders converge on the mesocorticolimbic DA system, which contains DRD1 and DRD2. The prior literature supports an association between DA receptor polymorphisms and opiate and cocaine dependence; it is unclear whether relationships exist between these same polymorphisms and HAND (Jacobs et al , 2012; Lawford et al , 2000; Li et al , 2006; Moyer et al , 2011; Noble et al , 1993; Perez de los Cobos et al , 2007; Persico et al , 1996; Shahmoradgoli Najafabadi et al , 2005). As substance dependence is a common feature of HIV populations, and may contribute to HAND through a variety of synergistic neurotoxicities, apportioning genetic risk is a complex problem.…”

Section: Discussionmentioning

confidence: 99%

“…Chronic cocaine and heroin users have decreased DA receptor availability and expression (Jacobs et al , 2012; Volkow et al , 1993; Volkow et al , 2007). Furthermore, these two substances have been consistently linked to genetic associations with SNPs of both DRD1 and DRD2 (Jacobs et al , 2012; Lawford et al , 2000; Li et al , 2006; Moyer et al , 2011; Noble et al , 1993; Perez de los Cobos et al , 2007; Persico et al , 1996; Shahmoradgoli Najafabadi et al , 2005). …”

Section: Introductionmentioning

confidence: 99%

HIV-related cognitive impairment shows bi-directional association with dopamine receptor DRD1 and DRD2 polymorphisms in substance-dependent and substance-independent populations

et al. 2013

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It has been postulated that drugs of abuse act synergistically with HIV, leading to increased neurotoxicity and neurocognitive impairment. The CNS impacts of HIV and drug use converge on the mesocorticolimbic dopamine (DA) system, which contains two main receptor subtypes: dopamine receptor 1 and 2. (DRD1, DRD2). DRD1 and DRD2 have been linked to substance dependence; whether they predict HIV-associated neurocognitive disorder (HAND) is unclear. Using an advanced-stage HIV+ population, we sought to determine if drug dependence impacts the contribution of DA receptor polymorphisms on neurocognition. We observed that both DRD1 and DRD2 polymorphisms were associated with opiate and cocaine dependence (P<0.05) in Caucasian subjects, but not African-American individuals. Using linear regression analysis, we examined the polymorphisms for associations with neuropsychological performance in global and cognitive domain T-scores (Motor, Processing Speed, Verbal Fluency, Learning, Memory, Executive Functioning, Working Memory) while controlling for opiate and cocaine dependency. In the Motor domain, we observed an association for two DRD2 polymorphisms (P<0.05) in Caucasian subjects. The effects differed for substance dependence groups as the direction of the correlations with DRD2 were opposite to what was seen in subjects without these dependencies. In African-American subjects, associations were observed in nearly every domain and again, the direction of the correlation differed between substance dependent and independent groups. We conclude that studies to examine genetic risk for HAND must carefully account for substance dependence patterns when assaying dopaminergic systems, as the neurobiological substrates of cognition in HIV populations may vary with tonic alterations secondary to chronic substance exposures.

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“…Dopamine receptor D2 (DRD2) is one of the most abundant receptors in central nervous system [27]. It has been suggested that this receptor is involved in reward-related psychiatric disorders [28], [29] such as addiction and schizophrenia [30], [31]. Studies have evidenced that the density and binding site of DRD2 are influenced by several functional polymorphisms in DRD2 [32], [33].…”

Section: Introductionmentioning

confidence: 99%

“…This polymorphism is related to the release of dopamine in the synaptic [34], [35], and T allele carriers are known to have a 30–40% decreased density of DRD2 [32], [34], [35]. Recent years, studies have indicated that TaqIA underlines the individual differences in work memory [36], sustained attention [37], [38], substance addiction [30], [39], and a reduced capacity in learning negative characteristics of stimuli [40]. However, the modulation of TaqIA on the attention to facial expressions, especially to the pleasure facial expressions, has not been well investigated.…”

Section: Introductionmentioning

confidence: 99%

Genetic Variations in COMT and DRD2 Modulate Attentional Bias for Affective Facial Expressions

et al. 2013

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Studies have revealed that catechol-O-methyltransferase (COMT) and dopaminegic receptor2 (DRD2) modulate human attention bias for palatable food or tobacco. However, the existing evidence about the modulations of COMT and DRD2 on attentional bias for facial expressions was still limited. In the study, 650 college students were genotyped with regard to COMT Val158Met and DRD2 TaqI A polymorphisms, and the attentional bias for facial expressions was assessed using the spatial cueing task. The results indicated that COMT Val158Met underpinned the individual difference in attentional bias for negative emotional expressions (P = 0.03) and the Met carriers showed more engagement bias for negative expressions than the Val/Val homozygote. On the contrary, DRD2 TaqIA underpinned the individual difference in attentional bias for positive expressions (P = 0.003) and individuals with TT genotype showed much more engagement bias for positive expressions than the individuals with CC genotype. Moreover, the two genes exerted significant interactions on the engagements for negative and positive expressions (P = 0.046, P = 0.005). These findings suggest that the individual differences in the attentional bias for emotional expressions are partially underpinned by the genetic polymorphisms in COMT and DRD2.

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Association between the DRD2 A1 allele and opium addiction in the Iranian population

Cited by 32 publications

References 24 publications

Overlapping Dopaminergic Pathway Genetic Susceptibility to Heroin and Cocaine Addictions in African Americans

Overlapping Dopaminergic Pathway Genetic Susceptibility to Heroin and Cocaine Addictions in African Americans

HIV-related cognitive impairment shows bi-directional association with dopamine receptor DRD1 and DRD2 polymorphisms in substance-dependent and substance-independent populations

Genetic Variations in COMT and DRD2 Modulate Attentional Bias for Affective Facial Expressions

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