A functional polymorphism in the monoamine oxidase A gene promoter
Open accessAbstract
We describe a new polymorphism upstream of the gene for monoamine oxidase A (MAOA), an important enzyme in human physiology and behavior. The polymorphism, which is located 1.2 kb upstream of the MAOA coding sequences, consists of a 30-bp repeated sequence present in 3, 3.5, 4, or 5 copies. The polymorphism is in linkage disequilibrium with other MAOA and MAOB gene markers and displays significant variations in allele frequencies across ethnic groups. The polymorphism has been shown to affect the transcriptional activity of the MAOA gene promoter by gene fusion and transfection experiments involving three different cell types. Alleles with 3.5 or 4 copies of the repeat sequence are transcribed 2-10 times more efficiently than those with 3 or 5 copies of the repeat, suggesting an optimal length for the regulatory region. This promoter region polymorphism may be useful as both a functional and an anonymous genetic marker for MAOA.
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Many studies regard the 2 R, 3 R, and 5 R MAOA-uVNTR repeats as low activity variants (MAOA-L), and the 3.5 R and 4 R repeats as high activity variants (MAOA-H).
“Many studies regard the 2 R, 3 R, and 5 R to be low activity variants (MAOA-L), and the 3.5 R and 4 R to be high activity variants (MAOA-H) [27].”
From Genetics of child aggression, a systematic review (2024) · cites this paper as [27]
“A VNTR upstream of MAOA” identifies 3, 3.5, 4, and 5 repeats, and “Effect on promoter function” reports higher transcription for the 3.5- and 4-repeat alleles than for the 3- and 5-repeat alleles. The paper does not identify or test a 2-repeat allele, so it does not support classifying 2R as low activity. It also reports its own experiments rather than establishing what many studies regard as the classification; page numbers were not available in the supplied copy. (LLM, conf=0.88)
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- Authors
- Sabol, S. Z., Hu, S., & Hamer, D.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- Hamer, D.
- ORCID
- Hamer, D.
- Venue
- Human Genetics
- Published
- 1998-09
- Volume
- 103
- Issue
- 3
- Pages
- 273-279
- ISSN
- 0018-7348 (ISSN-L)
- 0340-6717
- 1432-1203
- OpenAlex
- W2158955275
- Cited by
- 1,079
- References
- 46
- Citations by year
- 2026: 8 · 2025: 20 · 2024: 13 · 2023: 22 · 2022: 32 · 2021: 31 · 2020: 38 · 2019: 39 · 2018: 35 · 2017: 41 · 2016: 41 · 2015: 54 · 2014: 58 · 2013: 68 · 2012: 70
- FWCI
- 4.85
- Type
- journal article
- Language
- en
- Open access
- green
- zenodo.org
- Licence
- public-domain
- www.springer.com/tdm (tdm)
- Locations
- Human Genetics (publishedVersion)
- PubMed (publishedVersion)
- Zenodo (CERN European Organization for Nuclear Research) (submittedVersion, public-domain)
- 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 › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Keywords
- monoamine oxidase A, MAOA gene, promoter polymorphism, linkage disequilibrium, allele frequency variation, ethnic differences, transcriptional activity, gene fusion, transfection, genetic markers, gene expression regulation
- MeSH terms
- Adult, Alleles, Female, Genetic Markers, Haplotypes, Humans, Genetic Linkage, Male, Middle Aged, Monoamine Oxidase, Polymorphism, Genetic, Promoter Regions, Genetic, Minisatellite Repeats
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.
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