Association of the κ-opioid system with alcohol dependence

X Xuei; D Dick; L Flury-Wetherill; H-J Tian; A Agrawal; L Bierut; A Goate; K Bucholz; M Schuckit; J Nurnberger Jr; J Tischfield; S Kuperman; B Porjesz; H Begleiter; T Foroud; H J Edenberg

doi:10.1038/sj.mp.4001882

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Association of the κ-opioid system with alcohol dependence

Journal article

Peer reviewed

Association of the κ-opioid system with alcohol dependence

X Xuei, D Dick, L Flury-Wetherill, H-J Tian, A Agrawal, L Bierut, A Goate, K Bucholz, M Schuckit, J Nurnberger Jr, …

Molecular psychiatry, Vol.11(11), pp.1016-1024

08/22/2006

DOI: 10.1038/sj.mp.4001882

PMID: 16924269

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Abstract

Opioid receptors and their endogenous peptide ligands play important roles in the reward and reinforcement of drugs such as heroin, cocaine, and alcohol. The binding of dynorphins to the kappa-opioid receptor has been shown to produce aversive states, which may prevent the development of reinforcement. We genotyped SNPs throughout OPRK1, encoding the kappa-opioid receptor, and PDYN, which encodes its ligand prodynorphin, in a group of 1860 European American individuals from 219 multiplex alcohol dependent families. Family-based analyses demonstrated associations between alcohol dependence and multiple SNPs in the promoter and 3' end of PDYN, and in intron 2 of OPRK1. Haplotype analyses further supported the association of PDYN. Thus, variations in the genes encoding both the kappa-opioid receptor and its ligand, OPRK1 and PDYN, are associated with the risk for alcohol dependence; this makes biological sense as variations in either should affect signaling through the kappa-opioid system.

European Continental Ancestry Group - genetics

Genetic Predisposition to Disease

Protein Precursors - genetics

Enkephalins - metabolism

Humans

Risk Factors

Receptors, Opioid, kappa - metabolism

Linkage Disequilibrium

Protein Precursors - metabolism

Enkephalins - genetics

Haplotypes - genetics

Pedigree

Alcoholism - metabolism

Polymorphism, Single Nucleotide - genetics

Alcoholism - genetics

Receptors, Opioid, kappa - genetics

Details

Title: Subtitle: Association of the κ-opioid system with alcohol dependence
Creators: X Xuei - Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN 46202, USA. xxuei@iupui.edu
D Dick
L Flury-Wetherill
H-J Tian
A Agrawal
L Bierut
A Goate
K Bucholz
M Schuckit
J Nurnberger Jr
J Tischfield
S Kuperman
B Porjesz
H Begleiter
T Foroud
H J Edenberg
Resource Type: Journal article
Publication Details: Molecular psychiatry, Vol.11(11), pp.1016-1024
DOI: 10.1038/sj.mp.4001882
PMID: 16924269
NLM abbreviation: Mol Psychiatry
ISSN: 1359-4184
eISSN: 1476-5578
Publisher: England
Grant note: U10AA008401 / NIAAA NIH HHS
Language: English
Date published: 08/22/2006
Academic Unit: Psychiatry; Stead Family Department of Pediatrics
Record Identifier: 9984003938602771

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