title: Association of the PDYN gene with alcohol dependence and the propensity to drink in negative emotional states.
abstract: Synthetic κ-opioid receptor (KOR) agonists induce dysphoric and pro-depressive effects and variations in the KOR (OPRK1) and prodynorphin (PDYN) genes have been shown to be associated with alcohol dependence. We genotyped 23 single nucleotide polymorphisms (SNPs) in the PDYN and OPRK1 genes in 816 alcohol-dependent subjects and investigated their association with: (1) negative craving measured by a subscale of the Inventory of Drug Taking Situations; (2) a self-reported history of depression; (3) the intensity of depressive symptoms measured by the Beck Depression Inventory-II. In addition, 13 of the 23 PDYN and OPRK1 SNPs, which were previously genotyped in a set of 1248 controls, were used to evaluate association with alcohol dependence. SNP and haplotype tests of association were performed. Analysis of a haplotype spanning the PDYN gene (rs6045784, rs910080, rs2235751, rs2281285) revealed significant association with alcohol dependence (p = 0.00079) and with negative craving (p = 0.0499). A candidate haplotype containing the PDYN rs2281285-rs1997794 SNPs that was previously associated with alcohol dependence was also associated with negative craving (p = 0.024) and alcohol dependence (p = 0.0008) in this study. A trend for association between depression severity and PDYN variation was detected. No associations of OPRK1 gene variation with alcohol dependence or other studied phenotypes were found. These findings support the hypothesis that sequence variation in the PDYN gene contributes to both alcohol dependence and the induction of negative craving in alcohol-dependent subjects.
authors.affiliation: Psychiatry and Psychology, Mayo Clinic, Rochester, MN 55905, USA. karpyak.victor@mayo.edu
authors.forename: Victor M
authors.initials: VM
authors.lastname: Karpyak
authors.forename: Stacey J
authors.initials: SJ
authors.lastname: Winham
authors.forename: Ulrich W
authors.initials: UW
authors.lastname: Preuss
authors.forename: Peter
authors.initials: P
authors.lastname: Zill
authors.forename: Julie M
authors.initials: JM
authors.lastname: Cunningham
authors.forename: Denise L
authors.initials: DL
authors.lastname: Walker
authors.forename: Kriste A
authors.initials: KA
authors.lastname: Lewis
authors.forename: Jennifer R
authors.initials: JR
authors.lastname: Geske
authors.forename: Colin L
authors.initials: CL
authors.lastname: Colby
authors.forename: Osama A
authors.initials: OA
authors.lastname: Abulseoud
authors.forename: Daniel K
authors.initials: DK
authors.lastname: Hall-Flavin
authors.forename: Larissa L
authors.initials: LL
authors.lastname: Loukianova
authors.forename: Terry D
authors.initials: TD
authors.lastname: Schneekloth
authors.forename: Mark A
authors.initials: MA
authors.lastname: Frye
authors.forename: Igor
authors.initials: I
authors.lastname: Bazov
authors.forename: John A
authors.initials: JA
authors.lastname: Heit
authors.forename: Georgy
authors.initials: G
authors.lastname: Bakalkin
authors.forename: David A
authors.initials: DA
authors.lastname: Mrazek
authors.forename: Joanna M
authors.initials: JM
authors.lastname: Biernacka
mesh_terms: D000437:Alcoholism / Q000150:complications / Q000235:genetics*; D004745:Enkephalins / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D019964:Mood Disorders / Q000209:etiology / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011498:Protein Precursors / Q000235:genetics*; D017473:Receptors, Opioid, kappa / Q000235:genetics
chemical_list: D004745:Enkephalins; C515653:OPRK1 protein, human; D011498:Protein Precursors; D017473:Receptors, Opioid, kappa; C033660:preproenkephalin