Determination of methylated cpG sites in the promoter region of catechol-O-methyltransferase (COMT) and their involvement in the etiology of tobacco smoking
Open accessAbstract
We previously reported that catechol-O-methyltransferase (COMT) is significantly associated with nicotine dependence (ND) in humans. In this study, we examined whether there exists any difference in the extent of methylation of CpG dinucleotides in the promoter region of COMT in smokers and non-smokers by analyzing the methylation status of cytosines at 33 CpG sites through direct sequencing of bisulfite-treated DNA (N = 50 per group). The cytosine was methylated at 13 of 33 CpG sites, and two of these sites showed significant differences between smokers and matched non-smoker controls. Specifically, in the -193 CpG site, the degree of methylation was 19.1% in smokers and 13.2% in non-smokers (P < 0.01). This finding was confirmed by methylation-specific PCR using an additional 100 smoker and 100 non-smoker control samples, which showed the degree of methylation to be 22.2% in smokers and 18.3% in non-smokers (P < 0.01). For the -39 CpG site, the degree of methylation was 9.2% in smokers, whereas no methylation was found in non-smoker controls. Together, our findings provide the first molecular explanation at the epigenetic level for the association of ND with methylation of the COMT promoter, implying that methylation plays a role in smoking dependence.
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Cigarette smoking is associated with hypermethylation of the MB-COMT promoter.
“cigarette smoking is associated with hypermethylation of the MB-COMT promoter”
From The clinical use of epigenetics in psychiatry: a narrative review of epigenetic mechanisms, key candidate genes, and precision psychiatry (2025) · cites this paper as [80]
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- Authors
- Xu, Q.
- Affiliations
- Beijing Jiaotong University (CN)
- Corresponding author
- Xu, Qing
- ORCID
- Xu, Qing
- Venue
- Frontiers in Psychiatry
- Publisher
- Frontiers Media SA
- Published
- 2010
- Volume
- 1
- Pages
- 16-16
- ISSN
- 1664-0640 (ISSN-L)
- PMC
- PMC3059640
- OpenAlex
- W2069492893
- Cited by
- 32
- References
- 50
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 1 · 2023: 2 · 2022: 1 · 2021: 2 · 2019: 3 · 2018: 1 · 2017: 4 · 2015: 3 · 2014: 3 · 2013: 4 · 2012: 2
- FWCI
- 1.17
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Frontiers in Psychiatry (publishedVersion, cc-by)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institutes of Health
- National Institute on Drug Abuse (R01DA012844, R01DA013783)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Health Sciences › Medicine › Physiology › Smoking Behavior and Cessation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- catechol-O-methyltransferase, DNA methylation, CpG sites, nicotine dependence, smoking, epigenetics
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