The DOI matches its Crossref record; 32 of the 32 references it cites were found in a registry or an index.
The human dopamine D4 receptor repeat sequences modulate expression
Abstract
Genetic studies have implicated a polymorphic repeat sequence in exon 3 of the human dopamine D4 receptor in various behavioral and psychiatric disorders. Functionally various repeat variants are nearly identical, but whether these have different effects on gene expression has not been studied. To study the role of the repeat sequences on expression independently from its structural and functional effects at the protein level, we introduced these sequences immediately upstream of the promoter and in the 3' untranslated region of a luciferase reporter vector. In this report, we demonstrate that the repeat sequence can both modulate promoter activity and alter expression post-transcriptionally. The repeat sequence can serve as a substrate for a nuclear binding factor and all the three repeat variants can suppress promoter activity. Placement of the three repeat variants downstream from the luciferase gene in the expression vector shows, however, that the D4.7 repeat sequence has significantly suppressed expression of the reporter compared to the D4.2 and D4.4 repeats, likely via mechanisms involving RNA stability or translational efficiency. These data indicate that the various D4 repeat sequences have different effects on expression, which may explain its potential role in behavioral disorders.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Functional significance of this polymorphism has been demonstrated [70–75].”
From Genetics of child aggression, a systematic review (2024) · cites this paper as [73]
In the citing paper
“The 7 R has been shown to reduce in-vitro DRD4 expression [73] and to be less likely to form heterodimers with the dopamine D2 receptor [76], while the 4 R allele appears to be less responsive to quinpirole-mediated DRD4 upregulation [74].”
From Genetics of child aggression, a systematic review (2024) · cites this paper as [73]
In the citing paper
“and has been associated with increased reward related reactivity in ventral striatum, relative to the 4-repeat allele (Schoots and Van Tol 2003; Forbes, Brown et al. 2009; Stice, Yokum et al. 2012).”
From Developmental imaging genetics: Linking dopamine function to adolescent behavior (2014) · cites this paper as Schoots and Van Tol 2003
Citations
Cites
Dignam, J. D., Lebovitz, R. M., & Roeder, R. G. (1983) · Nucleic Acids Research · doi:10.1093/nar/11.5.1475 · Cited by 11,262
Firefly Luciferase Gene: Structure and Expression in Mammalian Cells
de Wet, J. R., Wood, K. V., DeLuca, M., Helinski, D. R., & Subramani, S. E. (1987) · Molecular and Cellular Biology · doi:10.1128/mcb.7.2.725 · Cited by 3,088
Multiple dopamine D4 receptor variants in the human population
Tol, H. H. M. V., Wu, C. M., Guan, H.-C., Ohara, K., Bunzow, J. R., Civelli, O., Kennedy, J., Seeman, P., Niznik, H. B., & Jovanovic, V. (1992) · Nature · doi:10.1038/358149a0 · Cited by 955
Modulation of intracellular cyclic AMP levels by different human dopamine D4 receptor variants
Asghari, V., Sanyal, S., Buchwaldt, S., Paterson, A., Jovanovic, V., & Van Tol, H. H. M. (1995) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1995.65031157.x · Cited by 858
Faraone, S., Doyle, A., Mick, E., & Biederman, J. (2001) · American Journal of Psychiatry · doi:10.1176/appi.ajp.158.7.1052 · Cited by 740
Dopamine D4 receptor gene polymorphism is associated with attention deficit hyperactivity disorder.
LaHoste, G. J., Swanson, J. M., Wigal, S. B., Glabe, C. G., Wigal, T. L., King, N., & Kennedy, J. L. (1996) · PubMed · Cited by 678
A hypervariable segment in the human dopamine receptor D4 (DRD4) gene
Lichter, J. B., Barr, C. L., Kennedy, J. L., Tol, H. H. M. V., Kídd, K. K., & Livak, K. J. (1993) · Human Molecular Genetics · doi:10.1093/hmg/2.6.767 · Cited by 524
Evidence of positive selection acting at the human dopamine receptor D4 gene locus
Ding, Y. C., Chi, H. C., Grady, D., Morishima, A., Kidd, J., Kidd, K., Flodman, P., Spence, M., Schuck, S., Swanson, J., et al. (2001) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.012464099 · Cited by 506
The poly(C)-binding proteins: A multiplicity of functions and a search for mechanisms
Makeyev, A. V., & Liebhaber, S. A. (2002) · RNA · doi:10.1017/s1355838202024627 · Cited by 469
The world-wide distribution of allele frequencies at the human dopamine D4 receptor locus
Chang, F., Kídd, K. K., Livak, K. J., PAKSTIS, A. J., & Kídd, K. K. (1996) · Human Genetics · doi:10.1007/s004390050166 · Cited by 438
Flagged first, then by citations
Cited by
Sorted by citations
Items 201–212 of 212
A study on candidate gene polymorphisms in association with mental retardation
Bhowmik, A. D. (2010) · Shodhganga
Using a Systems-Based Risk Score Approach to Examine Genetic Predisposition to Novelty Seeking
Conner, B. T., Hellemann, G., Demianczyk, A. C., Ritchie, T. L., & Noble, E. P. (2017) · Journal of Individual Differences · doi:10.1027/1614-0001/a000233
Az impulzivitás genetikai korrelátumai
Varga, G. (2015) · Eötvös Loránd Tudományegyetem · doi:10.15476/elte.2014.096
Challenges and Strategies for Integrating Molecular Genetics into Behavioral Science
Griffin, A. M., Schlomer, G. L., Vandenbergh, D. J., & Cleveland, H. H. (2019) · Emerging issues in family and individual resilience · doi:10.1007/978-3-030-05952-1_7
Journey from responsible alcohol drinking to alcoholism
Singh, A. K. (2020) · Elsevier eBooks · doi:10.1016/b978-0-12-819680-9.00001-9
Biological Determinants of Hostility
Гафаров, В. В., Громова, Е. А., Maksimov, V. N., Gagulin, I. V., & Гафарова, А. В. (2021) · IntechOpen eBooks · doi:10.5772/intechopen.97526
Elia, J., Sackett, J. C., Kurtz, N., de Berardinis, R., Larsen, L., Tang, S.-C., Hakonarson, H. H., & Nissley‐Tsiopinis, J. (2013) · doi:10.2217/ebo.13.190
Genetic susceptibility to peers
Schlomer, G. L., Griffin, A. M., Cleveland, H. H., & Vandenbergh, D. J. (2023) · Oxford University Press eBooks · doi:10.1093/oso/9780197602317.003.0012
Boroń, A., Recław, R., Chmielowiec, K., Chmielowiec, J., Strońska-Pluta, A., Kowalski, M. T., Masiak, J., Gibas-Dorna, M., Trybek, G., & Grzywacz, A. (2024) · Research Square · doi:10.21203/rs.3.rs-4409644/v1
Palumbo, S., Grassi, G., Mariotti, V., & Pellegrini, S. (2025) · Aggression and Violent Behavior · doi:10.1016/j.avb.2025.102096
Drawbacks in dopaminergic neurotransmission: compromising sexual performance
Armeni, A. K., Nappi, R. E., & Chedraui, P. (2026) · Gynecological Endocrinology · doi:10.1080/09513590.2026.2662695
Metadata
- Authors
- Schoots, O., & Van Tol, H. H. M.
- Affiliations
- Centre for Addiction and Mental Health (CA)
- Venue
- The Pharmacogenomics Journal
- Published
- 2003-10-28
- Volume
- 3
- Issue
- 6
- Pages
- 343-348
- ISSN
- 1470-269X (ISSN-L)
- 1473-1150
- OpenAlex
- W2015176102
- Cited by
- 213
- References
- 32
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 6 · 2023: 8 · 2022: 7 · 2021: 8 · 2020: 7 · 2019: 5 · 2018: 12 · 2017: 7 · 2016: 9 · 2015: 16 · 2014: 15 · 2013: 17 · 2012: 16
- FWCI
- 1.15
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Pharmacogenomics Journal (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Canada Research Chairs
- 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
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Keywords
- dopamine D4 receptor, DRD4, repeat polymorphism, exon 3, promoter activity, 3' untranslated region, post-transcriptional regulation, RNA stability, translation efficiency, gene expression regulation, mental illness
- MeSH terms
- Analysis of Variance, Gene Expression Regulation, HeLa Cells, Humans, Repetitive Sequences, Nucleic Acid, Receptors, Dopamine D2, Receptors, Dopamine D4
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
