HUMAN GENETIC STUDY: Association analysis of genes encoding the nociceptin receptor (<i>OPRL1</i>) and its endogenous ligand (<i>PNOC</i>) with alcohol or illicit drug dependence

Xuei, Xiaoling; Flury-Wetherill, Leah; Almasy, Laura; Bierut, Laura J.; Tischfield, Jay A.; Schuckit, Marc A.; Nürnberger, John I.; Foroud, Tatiana; Edenberg, Howard J.

doi:10.1111/j.1369-1600.2007.00082.x

Cited by 46 publications

(39 citation statements)

References 77 publications

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“…For example, Huang et al (2008) have reported a single-nucleotide polymorphism (SNP rs6010718) in the gene encoding the NOP receptor in alcohol-dependent individuals. In other studies, genetic variants of the OPRL1 gene were associated with opioid dependence (Xuei et al, 2008;Briant et al, 2010). In addition, increased vulnerability to alcohol dependence has been recently linked to DNA hypermethylation of the promoter regions of several genes, including the one encoding the NOP receptor suggesting the possibility that alcohol abuse is associated with a repressed NOP gene transcription (Zhang et al, 2013).…”

Section: Introductionmentioning

confidence: 93%

Genetic Deletion of the Nociceptin/Orphanin FQ Receptor in the Rat Confers Resilience to the Development of Drug Addiction

Kallupi

Scuppa

Guglielmo

et al. 2016

Neuropsychopharmacol

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The nociceptin (NOP) receptor is a G-protein-coupled receptor whose natural ligand is the NOP/orphanin FQ (N/OFQ) peptide. Evidence from pharmacological studies suggests that the N/OFQ system is implicated in the regulation of several addiction-related phenomena, such as drug intake, withdrawal, and relapse. Here, to further explore the role of NOP system in addiction, we used NOP (− / − ) rats to study the motivation for cocaine, heroin, and alcohol self-administration in the absence of N/OFQ function. Conditioned place preference (CPP) and saccharin (0.2% w/v) self-administration were also investigated. Results showed that NOP ( − / − ) rats selfadminister less cocaine (0.25, 0.125, or 0.5 mg/infusion) both under a fixed ratio 1 and a progressive ratio schedule of reinforcement compared with wild-type (Wt) controls. Consistently, cocaine (10 mg/kg, i.p.) was able to induce CPP in Wt but not in NOP ( − / − ). When NOP ( − / − ) rats were tested for heroin (20 μg/infusion) and ethanol (10% v/v) self-administration, they showed significantly lower drug intake compared with Wt. Conversely, saccharin self-administration was not affected by NOP deletion, excluding the possibility of nonspecific learning deficits or generalized disruption of reward mechanisms in NOP ( − / − ) rats. These findings were confirmed with pharmacological experiments using two selective NOP antagonists, SB-612111 and LY2817412. Both drugs attenuated alcohol selfadministration in Wt rats but not in NOP ( − / − ) rats. In conclusion, our results demonstrate that genetic deletion of NOP receptors confers resilience to drug abuse and support a role for NOP receptor antagonism as a potential treatment option for drug addiction.

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Section: Introductionmentioning

confidence: 93%

Genetic Deletion of the Nociceptin/Orphanin FQ Receptor in the Rat Confers Resilience to the Development of Drug Addiction

Kallupi

Scuppa

Guglielmo

et al. 2016

Neuropsychopharmacol

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“…On the other hand, SNPs within the NKAIN2 gene showed evidence of an association with neuroticism [50]. The OPRL1 gene encodes a G-protein-coupled receptor and may be involved in the regulation of numerous brain activities, particularly instinctive and emotional behaviors [51,52]. In addition, SNPs in the OPRL1 locus were associated with both alcohol and opioid dependence [51,52].…”

Section: Discussionmentioning

confidence: 99%

Interaction between Common Genetic Variants and Total Fat Intake on Low-Density Lipoprotein Peak Particle Diameter: A Genome-Wide Association Study

et al. 2015

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Background/Aim: Total fat intake has an important impact on the low-density lipoprotein (LDL) peak particle diameter (LDL-PPD) and may interact with nutrient-sensitive single nucleotide polymorphisms (SNPs). The objective wasto examine whether there is suggestive evidence of SNP × dietary fat intake interaction effects influencing the LDL-PPD in the Quebec Family Study (QFS) in order to generate hypotheses to be tested in larger studies. Methods: SNPs from a genome-wide association study (GWAS) using Illumina Human610-Quad BeadChip, total fat intake derived from a 3-day weighted food record, and SNP × total fat intake interaction effects were examined on LDL-PPD in 541 QFS subjects. Results: The GWAS analyses 29 identified independent SNP × total fat intake interaction effects on the LDL-PPD at p < 10^-5, including SNPs in the following genes: ABCG2, CPA3, FNBP1, KCNQ3, NBAS, NCALD, OPRL1, NKAIN2, SH3BGRL2, SOX5, and SUSD4. Conclusions: This observational study suggests that multiple SNPs interact with dietary fat intake to influence variation in the LDL-PPD.

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“…Two adjacent SNPs in intron 1 of OPRL1 were marginally associated with opioid dependence (rs6512305 (p=0.05), and rs6090043 (p=0.05)). However, neither gene showed association with both alcohol and opioid dependence (12).…”

Section: Xuei Et Al (2008) Conducted a Study On The Role Of The Nocmentioning

confidence: 88%

“…Seven studies investigated the role of genes in the opioid system (11)(12)(13)(14)(15)(16)(17)(18). Genes encoding all three types of opioid receptors were studied with variable results.…”

Section: Opioid Systemmentioning

confidence: 99%

Genetic pre-determinants of concurrent alcohol and opioid dependence: A critical review

Martin¹,

Klimas²,

Dunne³

et al. 2013

OA Alcohol

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Concurrent alcohol dependence poses a significant burden to health and wellbeing of people with established opioid dependence. Although previous research indicates that both genetic and environmental risk factors contribute to the development of drug or alcohol dependence, the role of genetic determinants in development of concurrent alcohol and opioid dependence has not been scrutinised.To search for genetic pre-determinants of concurrent alcohol and opioid dependence, electronic literature searches were completed using MEDLINE (PubMed) and EBSCO (Academic Search Complete) databases. Reference lists of included studies were also searched. In this discussion paper, we provide an overview of the genes (n=33) which are associated with the opioid, serotonergic, dopaminergic, GABA-ergic, cannabinoid, and metabolic systems for each dependency (i.e., alcohol or opioid) separately.The current evidence base is inconclusive regarding an exclusively genetic pre-determinant of concurrent alcohol and opioid dependence. Further search strategies and original research are needed to determine the genetic basis for concurrent alcohol and opioid dependency.

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HUMAN GENETIC STUDY: Association analysis of genes encoding the nociceptin receptor (OPRL1) and its endogenous ligand (PNOC) with alcohol or illicit drug dependence

Cited by 46 publications

References 77 publications

Genetic Deletion of the Nociceptin/Orphanin FQ Receptor in the Rat Confers Resilience to the Development of Drug Addiction

Genetic Deletion of the Nociceptin/Orphanin FQ Receptor in the Rat Confers Resilience to the Development of Drug Addiction

Interaction between Common Genetic Variants and Total Fat Intake on Low-Density Lipoprotein Peak Particle Diameter: A Genome-Wide Association Study

Genetic pre-determinants of concurrent alcohol and opioid dependence: A critical review

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