TY - JOUR
T1 - Association of the κ-opioid system with alcohol dependence
AU - Xuei, X.
AU - Dick, D.
AU - Flury-Wetherill, L.
AU - Tian, H. J.
AU - Agrawal, A.
AU - Bierut, L.
AU - Goate, A.
AU - Bucholz, K.
AU - Schuckit, M.
AU - Nurnberger, J.
AU - Tischfield, J.
AU - Kuperman, S.
AU - Porjesz, B.
AU - Begleiter, H.
AU - Foroud, T.
AU - Edenberg, H. J.
N1 - Funding Information:
We thank Jinghua Zhao, Gayathri Rajan, Christopher Rush, Jun Wang and Robert George for technical assistance with genotyping, sequencing and data organization. Genotyping facilities were provided by the Center for Medical Genomics at Indiana University School of Medicine, supported in part by the Indiana 21st Century Research and Technology Fund and the Indiana Genomics Initiative at Indiana University (INGEN, supported in part by the Lilly Endowment, Inc.). The Collaborative Study on the Genetics of Alcoholism (COGA), Co-Principal Investigators B Porjesz, V Hesselbrock, H Edenberg, L Bierut, includes nine different centers where data collection, analysis, and storage take place. The nine sites and Principal Investigators and Co-Investigators are: University of Connecticut (V Hesselbrock); Indiana University (HJ Edenberg, J Nurnberger Jr, PM Conneally, T Foroud); University of Iowa (S Kuperman, R Crowe); SUNY Downstate (B Porjesz); Washington University in St Louis (L Bierut, A Goate, J Rice); University of California at San Diego (M Schuckit); Howard University (R Taylor); Rutgers University (J Tischfield); Southwest Foundation (L Almasy). Zhaoxia Ren serves as the NIAAA Staff Collaborator. This national collaborative study is supported by the NIH Grant U10AA008401 from the National Institute on Alcohol Abuse and Alcoholism (NIAAA) and the National Institute on Drug Abuse (NIDA). In memory of Henri Begleiter and Theodore Reich, Principal and Co-Principal Investigators of COGA since its inception; we are indebted to their leadership in the establishment and nurturing of COGA, and acknowledge with great admiration their seminal scientific contributions to the field.
PY - 2006/11/27
Y1 - 2006/11/27
N2 - 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 κ-opioid receptor has been shown to produce aversive states, which may prevent the development of reinforcement. We genotyped SNPs throughout OPRK1, encoding the κ-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 κ-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 κ-opioid system.
AB - 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 κ-opioid receptor has been shown to produce aversive states, which may prevent the development of reinforcement. We genotyped SNPs throughout OPRK1, encoding the κ-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 κ-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 κ-opioid system.
KW - Alcoholism
KW - Dynorphin
KW - Genetics
KW - Opioids
KW - Single nucleotide polymorphism
KW - κ-opioid receptor
UR - http://www.scopus.com/inward/record.url?scp=33750319817&partnerID=8YFLogxK
U2 - 10.1038/sj.mp.4001882
DO - 10.1038/sj.mp.4001882
M3 - Article
C2 - 16924269
AN - SCOPUS:33750319817
SN - 1359-4184
VL - 11
SP - 1016
EP - 1024
JO - Molecular Psychiatry
JF - Molecular Psychiatry
IS - 11
ER -