Citations 2
Epigenetic and Transcriptional Control of the Opioid Prodynorphine Gene: In-Depth Analysis in the Human Brain
Nosova, Olga , Karpyak, Victor M. , Hallberg, Mathias , Bakalkin, Georgy , Karpyak, Victor , Hallberg, Mathias , Bakalkin, Georgy , Bazov, Igor
Molecules | June 7, 2021 | Volume: 26 | Issue: 11 | Pages: 3458
Neuropeptides serve as neurohormones and local paracrine regulators that control neural networks regulating behavior, endocrine system and sensorimotor functions. Their expression is characterized by exceptionally restricted profiles. Circuit-specific and adaptive expression of neuropeptide genes may be defined by transcriptional and epigenetic mechanisms controlled by cell type and subtype sequence-specific transcription factors, insulators and silencers. The opioid peptide dynorphins play a critical role in neurological and psychiatric disorders, pain processing and stress, while their mutations cause profound neurodegeneration in the human brain. In this review, we focus on the prodynorphin gene as a model for the in-depth epigenetic and transcriptional analysis of expression of the neuropeptide genes. Prodynorphin studies may provide a framework for analysis of mechanisms relevant for regulation of neuropeptide genes in normal and pathological human brain.
Association of the PDYN gene with alcohol dependence and the propensity to drink in negative emotional states
Karpyak, Victor M. , Winham, Stacey J. , Preuss, Ulrich W. , Zill, Peter , Cunningham, Julie M. , Walker, Denise L., Lewis, Kriste A., Geske, Jennifer R. , Colby, Colin , Hall‐Flavin, Daniel K., Loukianova, Larissa L., Schneekloth, Terry D. , Frye, Mark A. , Bazov, Igor , Heit, John A. , Bakalkin, Georgy , Mrazek, David A. , Abulseoud, Osama A. , Biernacka, Joanna M. , Winham, Stacey J , Karpyak, Victor , Bakalkin, Georgy , Geske, Jennifer
International Journal of Neuropsychopharmacology | October 29, 2012 | Volume: 16 | Issue: 5 | Pages: 975-985
AbstractSynthetic 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.