The DOI matches its Crossref record; 42 of the 42 references it cites were found in a registry or an index.
The single nucleotide polymorphism A118G alters functional properties of the human mu opioid receptor
Abstract
The most common single nucleotide polymorphism in the coding region of the human mu opioid receptor gene is the A118G variant, an adenine to guanine transition at nucleotide position 118 of the coding sequence of the gene. This polymorphism codes for an asparagine to aspartic acid substitution at amino acid 40 in the amino‐terminus, thereby removing a potential extracellular glycosylation site. Using in vitro cellular expression assays, this variant has been reported to change binding of the endogenous agonist beta‐endorphin and signaling of the receptor following binding of beta‐endorphin. Three clinical studies report that A118G genotype affects opioid antagonist‐mediated increases in cortisol levels. These studies demonstrate a functional role of this variant in responses to endogenous and exogenous opioids. To further characterize function, we expressed the prototype and variant receptors in two types of cells (human 293 embryonic kidney cells and Syrian hamster adenovirus‐12‐induced tumor cells). Stable expression of variant and prototype receptors was characterized by differences in levels of cell surface binding capacity (Bmax), forskolin‐induced cAMP accumulation, as well as agonist‐induced accumulation of cAMP (EC 50) for several agonists, but not for beta‐endorphin. In contrast, transiently expressed variant receptors showed only a minor difference in cell surface binding capacity compared to the prototype, and no differences in cAMP EC 50 values.
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“The A118G variant has enhanced binding and signaling properties, but low expression of mRNA (Zhang et al 2005; Kroslak et al 2007).”
From The behavioral, anatomical and pharmacological parallels between social attachment, love and addiction (2012) · cites this paper as Kroslak et al 2007
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Cites
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Self-citationKreek, M. J., Nielsen, D. A., Butelman, E. R., & LaForge, K. S. (2005) · Nature Neuroscience · doi:10.1038/nn1583 · Cited by 1,024
Self-citationOslin, D. W., Berrettini, W., Kranzler, H. R., Pettinati, H., Gelernter, J., Volpicelli, J. R., & O'Brien, C. P. (2003) · Neuropsychopharmacology · doi:10.1038/sj.npp.1300219 · Cited by 571
Allelic Expression Imbalance of Human mu Opioid Receptor (OPRM1) Caused by Variant A118G
Zhang, Y., Wang, D., Johnson, A. D., Papp, A. C., & Sadée, W. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m504942200 · Cited by 563
Sinha, R., Garcia, M., Paliwal, P., Kreek, M. J., & Rounsaville, B. J. (2006) · Archives of General Psychiatry · doi:10.1001/archpsyc.63.3.324 · Cited by 528
Self-citationPharmacogenetics and Human Molecular Genetics of Opiate and Cocaine Addictions and Their Treatments
Kreek, M. J., Bart, G., Lilly, C., Laforge, K. S., & Nielsen, D. A. (2005) · Pharmacological Reviews · doi:10.1124/pr.57.1.1 · Cited by 391
Self-citationKreek, M. J., LaForge, K. S., & Butelman, E. R. (2002) · Nature Reviews Drug Discovery · doi:10.1038/nrd897 · Cited by 371
Self-citationHoehe, M. R. (2000) · Human Molecular Genetics · doi:10.1093/hmg/9.19.2895 · Cited by 288
μ opioid receptor gene variants: lack of association with alcohol dependence
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Kreek, M. J., Proudnikov, D., Nielsen, D. A., & Yuferov, V. P. (2012) · Cambridge University Press eBooks · doi:10.1017/cbo9781139025997.025
Self-citationDroney, J. (2012) · Spiral (Imperial College London) · doi:10.25560/9252
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(2008) · Current Opinion in Neurology · doi:10.1097/wco.0b013e32831cbb85
Faculty Opinions recommendation of Mu opioids and their receptors: evolution of a concept.
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Wijekumar, P. J., Ranadeva, N. D. K., Jayamaha, A. R., Herath, H. M. N. D. M., Noorden, N., & Fernando, S. S. N. (2023) · Figshare · doi:10.6084/m9.figshare.24564122
Wijekumar, P. J., Ranadeva, N. D. K., Jayamaha, A. R., Herath, H. M. N. D. M., Noorden, N., & Fernando, S. S. N. (2024) · Figshare · doi:10.6084/m9.figshare.24564270
Dalvi, S., Halder, S., Kar, R., Kar, R., Gupta, R., Almeida, E. A., & Arora, G. (2026) · Pharmacogenomics · doi:10.1080/14622416.2026.2729995
Genetic variation in BDNF is associated with opioid use disorder severity
Kusic, D., Salzman, M., Heil, J., Grant, S. F. A., Trang, K. B., Zajic, S. C., Madžo, J., Brown, C., Jelı́nek, J., Calendo, G., et al. (2026) · Human Genetics · doi:10.1007/s00439-026-02866-x
“…receptor function, OUD association studies of these vari - ants have been less conclusive (Kember et al. 2022 ; Zhou et al. 2020 ; Moran et al. 2021 ; Zhang et al. 2005 ; Kroslak et al. 2007; Oertel et al. 2009 ; Deak et al. 2022a ; Schwantes-An et al. 2016 ; Burns et al. 2019 ; Mura et al. 2013).”
Metadata
- Authors
- Kroslak, T., LaForge, K. S., Gianotti, R. J., Ho, A., Nielsen, D. A., & Kreek, M. J.
- Affiliations
- Rockefeller University (US)
- Venue
- Journal of Neurochemistry
- Publisher
- Wiley
- Published
- 2007-06-03
- Volume
- 103
- Issue
- 1
- Pages
- 77-87
- ISSN
- 0022-3042 (ISSN-L)
- 1471-4159
- OpenAlex
- W2039877085
- Cited by
- 213
- References
- 42
- Citations by year
- 2026: 3 · 2024: 3 · 2023: 7 · 2022: 7 · 2021: 4 · 2020: 9 · 2019: 8 · 2018: 9 · 2017: 11 · 2016: 9 · 2015: 16 · 2014: 21 · 2013: 17 · 2012: 23
- FWCI
- 6.21
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neurochemistry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- Biotechnology and Biological Sciences Research Council (C17893)
- National Institute on Drug Abuse (R01DA012848, P60 DA 05130, P60DA005130, R01-DA-12848)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- mu-opioid receptor, A118G polymorphism, single nucleotide polymorphisms, cAMP signaling, forskolin, cell surface binding
- MeSH terms
- Cyclic AMP, Analgesics, Opioid, Animals, Binding, Competitive, Cell Line, Cell Membrane, Dose-Response Relationship, Drug, Fibroblasts, Colforsin, Cricetinae, Humans, Kidney, Mesocricetus, Receptors, Opioid, mu, Gene Transfer Techniques, Polymorphism, Single Nucleotide, Enkephalin, Ala(2)-MePhe(4)-Gly(5)-
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