Genetic association analyses of PDYN polymorphisms with heroin and cocaine addiction
Open accessAbstract
Genetic factors are believed to account for 30–50% of the risk for cocaine and heroin addiction. Dynorphin peptides, derived from the prodynorphin (PDYN) precursor, bind to opioid receptors, preferentially the kappa‐opioid receptor, and may mediate the aversive effects of drugs of abuse. Dynorphin peptides produce place aversion in animals and produce dysphoria in humans. Cocaine and heroin have both been shown to increase expression of PDYN in brain regions relevant for drug reward and use. Polymorphisms in PDYN are therefore hypothesized to increase risk for addiction to drugs of abuse. In this study, 3 polymorphisms in PDYN(rs1022563, rs910080 and rs1997794) were genotyped in opioid‐addicted [248 African Americans (AAs) and 1040 European Americans (EAs)], cocaine‐addicted (1248 AAs and 336 EAs) and control individuals (674 AAs and 656 EAs). Sex‐specific analyses were also performed as a previous study identified PDYN polymorphisms to be more significantly associated with female opioid addicts. We found rs1022563 to be significantly associated with opioid addiction in EAs [P= 0.03, odds ratio (OR) = 1.31; false discovery rate (FDR) corrected q‐value]; however, when we performed female‐specific association analyses, the OR increased from 1.31 to 1.51. Increased ORs were observed for rs910080 and rs199774 in female opioid addicts also in EAs. No statistically significant associations were observed with cocaine or opioid addiction in AAs. These data show that polymorphisms in PDYN are associated with opioid addiction in EAs and provide further evidence that these risk variants may be more relevant in females.
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Polymorphisms of the k-opioid receptor and prodynorphin genes are associated with higher risk for opioid addiction.
“Polymorphisms of the genes that encode the human k-opioid receptor (Yuferov et al., 2004;Gerra et al., 2007) and prodynorphin (Clarke et al., 2012) have also been associated with a higher risk for opioid addiction.”
From Drug Addiction: Hyperkatifeia/Negative Reinforcement as a Framework for Medications Development (2021) · cites this paper as Clarke et al., 2012
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Drug Addiction: Hyperkatifeia/Negative Reinforcement as a Framework for Medications Development
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- Authors
- Clarke, T. ‐., Ambrose‐Lanci, L., Ferraro, T. N., Berrettini, W. H., Kampman, K. M., Dackis, C. A., Pettinati, H. M., O’Brien, C. P., Oslin, D. W., & Lohoff, F. W.
- Affiliations
- University of Pennsylvania (US)
- Philadelphia VA Medical Center (US)
- Corresponding author
- Lohoff, F. W.
- Venue
- Genes, Brain and Behavior
- Publisher
- Wiley
- Published
- 2012-04-11
- Volume
- 11
- Issue
- 4
- Pages
- 415-423
- ISSN
- 1601-183X (ISSN-L)
- 1601-1848
- PMC
- PMC11987048
- OpenAlex
- W2083987763
- Cited by
- 55
- References
- 49
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 1 · 2023: 6 · 2022: 9 · 2021: 2 · 2020: 5 · 2019: 5 · 2018: 2 · 2017: 4 · 2016: 4 · 2015: 3 · 2014: 2 · 2013: 6 · 2012: 1
- FWCI
- 1.58
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genes Brain & Behavior (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- University of Pennsylvania
- National Institutes of Health (5p60da005186-25)
- National Institute of Mental Health (MH59566, MH-60870, MH-059565, MH067257, MH-061675, MH-59586, R01MH059566, R01MH059571, MH-059571, R01MH060879, R01MH059565, R01MH060870, T32MH014654, U01 MH-060879, R01MH061675, R01MH059586, R01MH059588, R01MH067257, MH-59587, MH 060879, MH-059588, K08MH080372, R01MH059587)
- National Institute on Drug Abuse (P60DA05186, P20DA025995, P60-DA005186, P50DA012756)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Keywords
- prodynorphin, heroin addiction, cocaine dependence, opioid use disorder, kappa opioid receptor, genetic susceptibility, sex differences, African Americans, European Americans
- MeSH terms
- Adolescent, Adult, Alleles, Black or African American, Enkephalins, Female, Gene Frequency, Genotype, Heroin Dependence, Humans, Male, Middle Aged, Protein Precursors, Sex Factors, Linkage Disequilibrium, Behavior, Addictive, Cocaine-Related Disorders, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, White People, Genetic Association Studies
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