DNA Hypermethylation of the Serotonin Receptor Type-2A Gene Is Associated with a Worse Response to a Weight Loss Intervention in Subjects with Metabolic Syndrome
Open accessAbstract
Understanding the regulation of gene activities depending on DNA methylation has been the subject of much recent study. However, although polymorphisms of the HTR2A gene have been associated with both obesity and psychiatric disorders, the role of HTR2A gene methylation in these illnesses remains uncertain. The aim of this study was to evaluate the association of HTR2A gene promoter methylation levels in white blood cells (WBC) with obesity traits and depressive symptoms in individuals with metabolic syndrome (MetS) enrolled in a behavioural weight loss programme. Analyses were based on 41 volunteers (mean age 49 ± 1 year) recruited within the RESMENA study. Depressive symptoms (as determined using the Beck Depression Inventory), anthropometric and biochemical measurements were analysed at the beginning and after six months of weight loss treatment. At baseline, DNA from WBC was isolated and cytosine methylation in the HTR2A gene promoter was quantified by a microarray approach. In the whole-study sample, a positive association of HTR2A gene methylation with waist circumference and insulin levels was detected at baseline. Obesity measures significantly improved after six months of dietary treatment, where a lower mean HTR2A gene methylation at baseline was associated with major reductions in body weight, BMI and fat mass after the treatment. Moreover, mean HTR2A gene methylation at baseline significantly predicted the decrease in depressive symptoms after the weight loss treatment. In conclusion, this study provides newer evidence that hypermethylation of the HTR2A gene in WBC at baseline is significantly associated with a worse response to a weight-loss intervention and with a lower decrease in depressive symptoms after the dietary treatment in subjects with MetS.
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Unbiased genome-wide studies using peripheral blood have reported epigenetic alterations in genes predominantly unassociated with established candidate genes such as SLC6A4 and BDNF.
“Unbiased, genome-wide studies using peripheral blood have reported epigenetic alterations in genes predominantly unassociated with established candidate genes selected based on known pathogenic findings, such as the serotonin transporter gene (SLC6A4) and brain-derived neurotrophic factor (BDNF),89–93”
From Epigenetic regulation in major depression and other stress-related disorders: molecular mechanisms, clinical relevance and therapeutic potential (2023) · cites this paper as [91]
The Methods (section 2.5; page not supplied) describe a blood-based methylation study using a 450K array, but the authors selected 20 CpG sites in HTR2A for analysis. This supports an alteration in a gene other than SLC6A4 or BDNF, not the claim that this was an unbiased genome-wide finding or that the reported genes were predominantly outside established candidates. (LLM, conf=0.84)
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“The strongest evidence is at the level of the serotonin transported genes (mainly SLC6A4) with candidate genes studies suggesting an increased in methylation in depression (Kang et al., 2013; Philibert et al., 2008; Zhao, Goldberg, Bremner, & Vaccarino, 2013), BD (Sugawara et al., 2011) and reporting a positive associ…”
BackgroundInfluential
- Authors
- Perez-Cornago, A., Mansego, M., Zulet, M., & Martinez, J.
- Affiliations
- Department of Nutrition, Food Science and Physiology, Center for Nutrition Research, University of Navarra, C/Irunlarrea 1, 31008-Pamplona, Spain
- Instituto de Salud Carlos III (ES)
- Venue
- Nutrients
- Publisher
- MDPI AG
- Published
- 2014-06-23
- Volume
- 6
- Issue
- 6
- Pages
- 2387-2403
- ISSN
- 2072-6643 (ISSN-L)
- PMC
- PMC4073158
- OpenAlex
- W2057943470
- Cited by
- 28
- References
- 52
- Citations by year
- 2025: 1 · 2024: 4 · 2023: 1 · 2022: 3 · 2021: 2 · 2020: 1 · 2019: 2 · 2018: 3 · 2017: 6 · 2016: 1 · 2015: 2 · 2014: 1
- FWCI
- 1.37
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Nutrients (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Deposito Adademico Digital Universidad De Navarra (University of Navarra) (submittedVersion, other-oa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Universidad de Navarra (LE/97)
- Gobierno de Navarra (LE/97)
- Asociación de Amigos de la Universidad de Navarra
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Nutrition, Genetics, and Disease
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- HTR2A, DNA methylation, promoter hypermethylation, metabolic syndrome, weight loss interventions, dietary therapy, obesity, depressive symptoms, leukocytes, epigenetics, insulin, waist circumference, body mass index, fat mass
- MeSH terms
- Anthropometry, Base Sequence, Blood Pressure, Diet, Reducing, Gene Expression Regulation, Humans, Middle Aged, Molecular Sequence Data, Promoter Regions, Genetic, Receptors, Serotonin, Weight Loss, DNA Methylation, Metabolic Syndrome, Receptor, Serotonin, 5-HT2A, Real-Time Polymerase Chain Reaction
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