Pre-operative DNA methylation marks as predictors of weight loss outcomes after sleeve gastrectomy

Objective: Although DNA methylation has been suggested to be a potential predictor of the progression of obesity and obesity-related diseases, little is known about its potential role as predictive marker of successful weight loss after bariatric surgery. Methods: 20 patients who underwent sleeve ga...

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Main Authors: Guillermo Paz-López, Teresa M. Linares-Pineda, Andrés González-Jiménez, Raquel Sancho-Marín, Luis Ocaña-Wilhelmi, Francisco J. Tinahones, Sonsoles Morcillo, Carolina Gutiérrez-Repiso
Format: Article
Language:English
Published: Elsevier 2025-02-01
Series:Molecular Metabolism
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Online Access:http://www.sciencedirect.com/science/article/pii/S2212877824002187
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author Guillermo Paz-López
Teresa M. Linares-Pineda
Andrés González-Jiménez
Raquel Sancho-Marín
Luis Ocaña-Wilhelmi
Francisco J. Tinahones
Sonsoles Morcillo
Carolina Gutiérrez-Repiso
author_facet Guillermo Paz-López
Teresa M. Linares-Pineda
Andrés González-Jiménez
Raquel Sancho-Marín
Luis Ocaña-Wilhelmi
Francisco J. Tinahones
Sonsoles Morcillo
Carolina Gutiérrez-Repiso
author_sort Guillermo Paz-López
collection DOAJ
description Objective: Although DNA methylation has been suggested to be a potential predictor of the progression of obesity and obesity-related diseases, little is known about its potential role as predictive marker of successful weight loss after bariatric surgery. Methods: 20 patients who underwent sleeve gastrectomy were classified according to the percentage of excess weight loss (%EWL) 1 year after bariatric surgery, using 60% as the cut-off point. Blood DNA methylation was analyzed prior to surgery using the Infinium Methylation EPIC Bead Chip array-based platform. Results: A total number of 76,559 differentially methylated positions (DMPs) (p < 0.05) were found between <60% EWL and >60% EWL groups. Of them, 59,308 DMPs were annotated to genes. KEGG enrichment analysis showed that pathways involved in the signalling of MAPK, Wnt, mTor, FoxO and AMPK, among others, were involved in weight loss trajectory.A stepwise logistic regression using the DMPs with an absolute Δβ >0.2 showed that higher methylation levels in the CpG sites cg02405213 (mapping to JAK2) (OR: 1.20098, [0.9586, 1.5044]) and cg01702330 (OR: 2.4426, [0.5761, 10.3567]), were shown to be associated with a higher probability of achieving >60 %EWL after sleeve gastrectomy, whereas higher methylation levels in the CpG site cg04863892 (mapping to HOXA5) were associated with lower probability of achieving >60 %EWL after sleeve gastrectomy (OR: 0.7966, [0.5637, 1.1259]). Conclusions: Our results show a different pre-surgery methylation pattern according to %EWL. We identified three CpG sites (cg04863892, cg02405213, cg01702330) with potential value as predictor markers of weight loss response to bariatric surgery.
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spelling doaj-art-29e43768924c4553917c91e22b1746f22025-02-01T04:11:57ZengElsevierMolecular Metabolism2212-87782025-02-0192102087Pre-operative DNA methylation marks as predictors of weight loss outcomes after sleeve gastrectomyGuillermo Paz-López0Teresa M. Linares-Pineda1Andrés González-Jiménez2Raquel Sancho-Marín3Luis Ocaña-Wilhelmi4Francisco J. Tinahones5Sonsoles Morcillo6Carolina Gutiérrez-Repiso7Estructura Común de Apoyo a la Investigación de Bioinformática. Instituto de Investigación Biomédica de Málaga-Plataforma BIONAND (IBIMA-Plataforma Bionand), Málaga, SpainInstituto de Investigación Biomédica de Málaga-Plataforma BIONAND (IBIMA-Plataforma Bionand), Málaga, Spain; Unidad de Gestión Clínica de Endocrinología y Nutrición, Hospital Universitario Virgen de la Victoria de Málaga, Málaga, SpainEstructura Común de Apoyo a la Investigación de Bioinformática. Instituto de Investigación Biomédica de Málaga-Plataforma BIONAND (IBIMA-Plataforma Bionand), Málaga, SpainInstituto de Investigación Biomédica de Málaga-Plataforma BIONAND (IBIMA-Plataforma Bionand), Málaga, Spain; Unidad de Gestión Clínica de Endocrinología y Nutrición, Hospital Universitario Virgen de la Victoria de Málaga, Málaga, SpainInstituto de Investigación Biomédica de Málaga-Plataforma BIONAND (IBIMA-Plataforma Bionand), Málaga, Spain; Unidad de Gestión Clínica de Cirugía General, Digestiva y Trasplantes, Hospital Universitario Virgen de la Victoria, Málaga, Spain; Departamento de Especialidades Quirúrgicas, Bioquímica e Inmunología, Universidad de Málaga, Málaga, SpainInstituto de Investigación Biomédica de Málaga-Plataforma BIONAND (IBIMA-Plataforma Bionand), Málaga, Spain; Unidad de Gestión Clínica de Endocrinología y Nutrición, Hospital Universitario Virgen de la Victoria de Málaga, Málaga, Spain; Centro de Investigación Biomédica en Red de la Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain; Departamento de Medicina y Dermatología. Facultad de Medicina. Universidad de Málaga, Málaga, Spain; Corresponding author. Instituto de Investigación Biomédica de Málaga-Plataforma BIONAND (IBIMA-Plataforma Bionand), Málaga, Spain.Instituto de Investigación Biomédica de Málaga-Plataforma BIONAND (IBIMA-Plataforma Bionand), Málaga, Spain; Unidad de Gestión Clínica de Endocrinología y Nutrición, Hospital Universitario Virgen de la Victoria de Málaga, Málaga, Spain; Centro de Investigación Biomédica en Red de la Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain; Corresponding author. Unidad de Gestión Clínica de Endocrinología y Nutrición, Hospital Universitario Virgen de la Victoria, Campus de Teatinos s/n, 29010 Málaga, Spain.Instituto de Investigación Biomédica de Málaga-Plataforma BIONAND (IBIMA-Plataforma Bionand), Málaga, Spain; Unidad de Gestión Clínica de Endocrinología y Nutrición, Hospital Universitario Virgen de la Victoria de Málaga, Málaga, Spain; Centro de Investigación Biomédica en Red de la Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, SpainObjective: Although DNA methylation has been suggested to be a potential predictor of the progression of obesity and obesity-related diseases, little is known about its potential role as predictive marker of successful weight loss after bariatric surgery. Methods: 20 patients who underwent sleeve gastrectomy were classified according to the percentage of excess weight loss (%EWL) 1 year after bariatric surgery, using 60% as the cut-off point. Blood DNA methylation was analyzed prior to surgery using the Infinium Methylation EPIC Bead Chip array-based platform. Results: A total number of 76,559 differentially methylated positions (DMPs) (p < 0.05) were found between <60% EWL and >60% EWL groups. Of them, 59,308 DMPs were annotated to genes. KEGG enrichment analysis showed that pathways involved in the signalling of MAPK, Wnt, mTor, FoxO and AMPK, among others, were involved in weight loss trajectory.A stepwise logistic regression using the DMPs with an absolute Δβ >0.2 showed that higher methylation levels in the CpG sites cg02405213 (mapping to JAK2) (OR: 1.20098, [0.9586, 1.5044]) and cg01702330 (OR: 2.4426, [0.5761, 10.3567]), were shown to be associated with a higher probability of achieving >60 %EWL after sleeve gastrectomy, whereas higher methylation levels in the CpG site cg04863892 (mapping to HOXA5) were associated with lower probability of achieving >60 %EWL after sleeve gastrectomy (OR: 0.7966, [0.5637, 1.1259]). Conclusions: Our results show a different pre-surgery methylation pattern according to %EWL. We identified three CpG sites (cg04863892, cg02405213, cg01702330) with potential value as predictor markers of weight loss response to bariatric surgery.http://www.sciencedirect.com/science/article/pii/S2212877824002187DNA methylationSleeve gastrectomyWeight lossPredictive biomarker
spellingShingle Guillermo Paz-López
Teresa M. Linares-Pineda
Andrés González-Jiménez
Raquel Sancho-Marín
Luis Ocaña-Wilhelmi
Francisco J. Tinahones
Sonsoles Morcillo
Carolina Gutiérrez-Repiso
Pre-operative DNA methylation marks as predictors of weight loss outcomes after sleeve gastrectomy
Molecular Metabolism
DNA methylation
Sleeve gastrectomy
Weight loss
Predictive biomarker
title Pre-operative DNA methylation marks as predictors of weight loss outcomes after sleeve gastrectomy
title_full Pre-operative DNA methylation marks as predictors of weight loss outcomes after sleeve gastrectomy
title_fullStr Pre-operative DNA methylation marks as predictors of weight loss outcomes after sleeve gastrectomy
title_full_unstemmed Pre-operative DNA methylation marks as predictors of weight loss outcomes after sleeve gastrectomy
title_short Pre-operative DNA methylation marks as predictors of weight loss outcomes after sleeve gastrectomy
title_sort pre operative dna methylation marks as predictors of weight loss outcomes after sleeve gastrectomy
topic DNA methylation
Sleeve gastrectomy
Weight loss
Predictive biomarker
url http://www.sciencedirect.com/science/article/pii/S2212877824002187
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