Differentially methylated regions (DMRs) in PON3 gene between responders and non-responders to a weight loss dietary intervention: a new tool for precision management of obesity
Open accessAbstract
Differentially methylated regions (DMR) are genomic regions with different methylation status. The aim of this research was to identify DMRs in subjects with obesity that predict the response to a weight-loss dietary intervention and its association with metabolic variables. Based on the change in body mass index (BMI), 201 subjects with overweight and obesity were categorized in tertiles according to their response to a hypocaloric diet: Responders (R; n = 64) and Non-Responders (NR; n = 63). The R group lost 4.55 ± 0.91 BMI units (kg/m2) and the NR group lost 1.95 ± 0.73 kg/m2 (p < 0.001). DNA methylation was analysed in buffy coat through a methylation array at baseline. DMRs were analysed using a function of ChAMP (Chip Analysis Methylation Pipeline) in R software. Baseline DNA methylation analysis between R and NR exhibited a DMR located at paraoxonase 3 gene (PON3) consisting of 13 CpG sites, eleven of them significantly hypermethylated in R. To analyse the implication of these 11 CpGs on weight loss, a z-score was performed as a measure of DMR methylation. This analysis showed a correlation between PON3 DNA methylation and BMI loss. This z-score negatively correlated with PON3 protein serum levels. Total paraoxonase activity in serum was not different between groups, but PON enzymatic activity positively correlated with oxidized LDL levels. The present study identified a DMR within PON3 gene that is related to PON3 protein levels in serum, and that could be used as a potential biomarker to predict the response to weight-loss dietary interventions.
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In non-invasive brain stimulation and other intervention studies, non-responders are routinely excluded or treated differently.
“in non-invasive brain stimulation studies84,85 or other intervention studies, such as those focusing on physical exercise or nutrition86–89, ‘non-responders’ are routinely excluded from data analyses or treated differently.”
From Near transfer to an unrelated N-back task mediates the effect of N-back working memory training on matrix reasoning (2022) · cites this paper as [87]
The Study design section (page unavailable) says this dietary-intervention study separated responders from non-responders for analysis, supporting the claim that they were treated differently in this instance. It did not exclude non-responders: it excluded participants with poor dietary adherence and those in the intermediate response tertile. One study also cannot establish that this practice is routine, and this paper does not address brain stimulation. (LLM, conf=0.84)
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- Authors
- Salas-Pérez, F., Cuevas-Sierra, A., Cuervo, M., Goni, L., Milagro, F. I., Martínez, J. A., & Riezu-Boj, J. I.
- Affiliations
- Department of Nutrition, Food Science and Physiology, Center for Nutrition Research, University of Navarra, Pamplona, Spain
- Navarre Institute of Health Research (ES)
- IdiSNA, Navarra Institute for Health Research, Pamplona, Spain
- Instituto de Salud Carlos III (ES)
- ORCID
- Venue
- Epigenetics
- Publisher
- Informa UK Limited
- Published
- 2021-01-25
- Volume
- 17
- Issue
- 1
- Pages
- 81-92
- ISSN
- 1559-2294 (ISSN-L)
- 1559-2308
- PMC
- PMC8812777
- OpenAlex
- W3118998628
- Cited by
- 16
- References
- 45
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 4 · 2023: 2 · 2022: 1 · 2021: 4
- FWCI
- 0.86
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Epigenetics (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- Gobierno de Navarra (CB12/03/30002, PT024)
- Comisión Nacional de Investigación Científica y Tecnológica (CB12/03/30002)
- 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
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Paraoxonase enzyme and polymorphisms
- Keywords
- differentially methylated regions, PON3, DNA methylation, obesity, hypocaloric diet, treatment response prediction, biomarkers, CpG hypermethylation, body mass index, oxidized LDL, paraoxonase activity, precision medicine
- MeSH terms
- Diet, Reducing, Humans, Obesity, Weight Loss, Body Mass Index, DNA Methylation, Aryldialkylphosphatase
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