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

IF 7 2区医学 Q1 ENDOCRINOLOGY & METABOLISM

Molecular Metabolism Pub Date : 2025-02-01 DOI:10.1016/j.molmet.2024.102087

Guillermo Paz-López , Teresa M. Linares-Pineda , Andrés González-Jiménez , Raquel Sancho-Marín , Luis Ocaña-Wilhelmi , Francisco J. Tinahones , Sonsoles Morcillo , Carolina Gutiérrez-Repiso

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引用次数: 0

Abstract

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.

查看原文本刊更多论文

术前DNA甲基化标记作为袖式胃切除术后体重减轻结果的预测因子。

虽然DNA甲基化已被认为是肥胖和肥胖相关疾病进展的潜在预测因子，但其作为减肥手术后成功减肥的预测标志物的潜在作用知之甚少。材料与方法：根据减重术后1年超重减重百分比（%EWL）对20例行袖胃切除术的患者进行分类，以60%为分界点。在手术前使用基于Infinium甲基化EPIC头芯片阵列的平台分析血液DNA甲基化。结果：共有76,559个差异甲基化位点（dmp）（占EWL组的60%）。其中，59,308个dmp被注释到基因上。KEGG富集分析表明，MAPK、Wnt、mTor、FoxO和AMPK等信号通路参与了体重减轻的轨迹。使用绝对值Δβ >0.2的dmp逐步逻辑回归显示，CpG位点cg02405213（映射到JAK2）（OR: 1.20098,[0.9586, 1.5044]）和cg01702330 (OR：2.4426,[0.5761, 10.3567])与套筒胃切除术后> 60% EWL的较高概率相关，而CpG位点cg04863892（定位于HOXA5）的较高甲基化水平与套筒胃切除术后> 60% EWL的较低概率相关（OR: 0.7966,[0.5637, 1.1259]）。结论：我们的结果显示术前甲基化模式根据%EWL不同。我们确定了三个CpG位点（cg04863892, cg02405213, cg01702330），它们可能作为减肥手术后体重减轻反应的预测指标。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Molecular Metabolism ENDOCRINOLOGY & METABOLISM-

CiteScore

14.50

自引率

2.50%

发文量

219

审稿时长

43 days

期刊介绍： Molecular Metabolism is a leading journal dedicated to sharing groundbreaking discoveries in the field of energy homeostasis and the underlying factors of metabolic disorders. These disorders include obesity, diabetes, cardiovascular disease, and cancer. Our journal focuses on publishing research driven by hypotheses and conducted to the highest standards, aiming to provide a mechanistic understanding of energy homeostasis-related behavior, physiology, and dysfunction. We promote interdisciplinary science, covering a broad range of approaches from molecules to humans throughout the lifespan. Our goal is to contribute to transformative research in metabolism, which has the potential to revolutionize the field. By enabling progress in the prognosis, prevention, and ultimately the cure of metabolic disorders and their long-term complications, our journal seeks to better the future of health and well-being.