title: Association of the kappa-opioid system with alcohol dependence.
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.
authors.affiliation: Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN 46202, USA. xxuei@iupui.edu
authors.forename: X
authors.initials: X
authors.lastname: Xuei
authors.forename: D
authors.initials: D
authors.lastname: Dick
authors.forename: L
authors.initials: L
authors.lastname: Flury-Wetherill
authors.forename: H-J
authors.initials: HJ
authors.lastname: Tian
authors.forename: A
authors.initials: A
authors.lastname: Agrawal
authors.forename: L
authors.initials: L
authors.lastname: Bierut
authors.forename: A
authors.initials: A
authors.lastname: Goate
authors.forename: K
authors.initials: K
authors.lastname: Bucholz
authors.forename: M
authors.initials: M
authors.lastname: Schuckit
authors.forename: J
authors.initials: J
authors.lastname: Nurnberger
authors.forename: J
authors.initials: J
authors.lastname: Tischfield
authors.forename: S
authors.initials: S
authors.lastname: Kuperman
authors.forename: B
authors.initials: B
authors.lastname: Porjesz
authors.forename: H
authors.initials: H
authors.lastname: Begleiter
authors.forename: T
authors.initials: T
authors.lastname: Foroud
authors.forename: H J
authors.initials: HJ
authors.lastname: Edenberg
mesh_terms: D000437:Alcoholism / Q000235:genetics* / Q000378:metabolism; D004745:Enkephalins / Q000235:genetics* / Q000378:metabolism; D020022:Genetic Predisposition to Disease; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D015810:Linkage Disequilibrium; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011498:Protein Precursors / Q000235:genetics* / Q000378:metabolism; D017473:Receptors, Opioid, kappa / Q000235:genetics* / Q000378:metabolism; D012307:Risk Factors; D044465:White People / Q000235:genetics
chemical_list: D004745:Enkephalins; C515653:OPRK1 protein, human; D011498:Protein Precursors; D017473:Receptors, Opioid, kappa; C116587:kappa(1) opioid receptor; C033660:preproenkephalin