The quantification of COMT mRNA in post mortem cerebellum tissue: diagnosis, genotype, methylation and expression
Open accessAbstract
Background: The COMT gene is located on chromosome 22q11, a region strongly implicated in the aetiology of several psychiatric disorders, in particular schizophrenia. Previous research has suggested that activity and expression of COMT is altered in schizophrenia, and is mediated by one or more polymorphisms within the gene, including the functional Val 158 Met polymorphism. Method: In this study we examined the expression levels of COMT mRNA using quantitative RT-PCR in 60 post mortem cerebellum samples derived from individuals with schizophrenia, bipolar disorder, depression, and no history of psychopathology. Furthermore, we have examined the methylation status of two CpG sites in the promoter region of the gene. Results: We found no evidence of altered COMT expression or methylation in any of the psychiatric diagnoses examined. We did, however, find evidence to suggest that genotype is related to COMT gene expression, replicating the findings of two previous studies. Specifically, val 158 met (rs165688; Val allele) rs737865 (G allele) and rs165599 (G allele) all showed reduced expression (P < 0.05). Finally, we observe a strong sexual dimorphism in COMT expression, with females exhibiting significantly greater levels of COMT mRNA. Conclusion: The expression of COMT does not appear to be altered in the cerebellum of individuals suffering from schizophrenia, bipolar disorder or depression, but does appear to be influenced by single nucleotide polymorphisms within the gene.
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COMTVal158Met is differentially expressed across genders.
“This is consistent with evidence that COMTVal158Met is differentially expressed across genders (Dempster et al, 2006; Gogos et al, 1998).”
From DAT1 and COMT effects on delay discounting and trait impulsivity in male adolescents with attention deficit/hyperactivity disorder and healthy controls (2010) · cites this paper as Dempster et al, 2006
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- Authors
- Dempster, E. L., Mill, J., Craig, I. W., & Collier, D. A.
- Affiliations
- King's College London (GB)
- Corresponding author
- Dempster, Emma L
- Venue
- BMC Medical Genetics
- Published
- 2006-02-16
- Volume
- 7
- Issue
- 1
- Pages
- 10-10
- ISSN
- 1471-2350 (ISSN-L)
- PMC
- PMC1456954
- OpenAlex
- W1607356988
- Cited by
- 129
- References
- 38
- Citations by year
- 2026: 1 · 2025: 2 · 2023: 2 · 2022: 5 · 2021: 4 · 2020: 5 · 2019: 1 · 2018: 4 · 2017: 6 · 2016: 4 · 2015: 9 · 2014: 11 · 2013: 6 · 2012: 17
- FWCI
- 6.39
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- BMC Medical Genetics (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Research Portal (King's College London) (submittedVersion)
- Funders
- Stanley Medical Research Institute
- Medical Research Council
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Keywords
- COMT gene, cerebellum, schizophrenia, bipolar disorder, depression, COMT Val158Met polymorphism, single nucleotide polymorphisms, DNA methylation, promoter CpG sites, genotypes, sexual dimorphism, chromosome 22q11
- MeSH terms
- Mental Disorders, Bipolar Disorder, Catechol O-Methyltransferase, Cerebellum, Depressive Disorder, Female, Genotype, Humans, Male, RNA, Messenger, Schizophrenia, Sex Characteristics, Gene Expression, DNA Methylation, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide
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