Pharmacogenomics: Catechol-O-methyltransferase to thiopurine S-methyltransferase
Open accessAbstract
1. Pharmacogenomics is the study of the role of inheritance in variation in the drug response phenotype-a phenotype that can vary from adverse drug reactions at one end of the spectrum to lack of therapeutic efficacy at the other. 2. The thiopurine S-methyltransferase (TPMT) genetic polymorphism represents one of the best characterized and most clinically relevant examples of pharmacogenomics. This polymorphism has also served as a valuable "model system" for studies of the ways in which variation in DNA sequence might influence function. 3. The discovery and characterization of the TPMT polymorphism grew directly out of pharmacogenomic studies of catechol O-methyltransferase (COMT), an enzyme discovered by Julius (Julie) Axelrod and his coworkers. 4. This review will outline the process by which common, functionally significant genetic polymorphisms for both COMT and TPMT were discovered and will use these two methyltransferase enzymes to illustrate general principles of pharmacogenomic research-both basic mechanistic and clinical translational research-principles that have been applied to a series of genes encoding methyltransferase enzymes.
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The rs4680 Val158Met SNP leads to reduced COMT enzymatic activity in Met carriers.
“The common rs4680 Val 158 Met single nucleotide polymorphism (SNP) leads to a reduction of COMT enzymatic activity in Met carriers (6-8).”
From Influence of the COMT genotype on working memory and brain activity changes during development (2011) · cites this paper as [8]
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Influence of the COMT genotype on working memory and brain activity changes during development
Dumontheil, I., Roggeman, C., Ziermans, T., Peyrard-Janvid, M., Matsson, H., Kere, J., & Klingberg, T. (2011) · Biological Psychiatry · doi:10.1016/j.biopsych.2011.02.027 · Cited by 165 · see citing works
- Authors
- Weinshilboum, R. M.
- Affiliations
- Mayo Clinic (US)
- Corresponding author
- Weinshilboum, Richard M.
- Venue
- Cellular and Molecular Neurobiology
- Published
- 2006-06-29
- Volume
- 26
- Issue
- 4-6
- Pages
- 537-559
- ISSN
- 0272-4340 (ISSN-L)
- 1573-6830
- PMC
- PMC11520626
- OpenAlex
- W2020153758
- Cited by
- 66
- References
- 86
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 2 · 2023: 1 · 2022: 4 · 2021: 2 · 2020: 3 · 2019: 2 · 2018: 4 · 2017: 6 · 2016: 2 · 2015: 2 · 2013: 4 · 2012: 7
- FWCI
- 0.65
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Cellular and Molecular Neurobiology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of General Medical Sciences (U-01 GM61388, R01-GM-28157, R01 GM 35720, U01GM061388, R01GM028157, R01GM035720)
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Glutathione Transferases and Polymorphisms
- Keywords
- pharmacogenomics, catechol-O-methyltransferase, thiopurine S-methyltransferase, genetic polymorphism, drug response variability, adverse drug reactions, treatment efficacy
- MeSH terms
- Animals, Catechol O-Methyltransferase, Humans, Inactivation, Metabolic, Methylation, Methyltransferases, Models, Biological, Pharmacogenetics, Polymorphism, Genetic
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