DNA methylation is differentially associated with glycemic outcomes by different types of weight-loss interventions: an epigenome-wide association study.

IF 5.7 2区 医学 Q1 Medicine
Xiaoxiao Wen, Helena Palma-Gudiel, Guanhong Miao, Mingjing Chen, Zhiguang Huo, Hao Peng, Stephen Anton, Gang Hu, Ricky Brock, Phillip J Brantley, Jinying Zhao
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引用次数: 0

Abstract

Background: Alterations in DNA methylation (DNAm) have been reported to be a mechanism by which bariatric surgeries resulted in considerable metabolic improvements. Previous studies have mostly focused on change in DNAm following weight-loss interventions, yet whether DNAm prior to intervention can explain the variability in glycemic outcomes has not been investigated. Here, we aim to examine whether baseline DNAm is differentially associated with glycemic outcomes induced by different types of weight-loss interventions.

Methods: Participants were 75 adults with severe obesity who underwent non-surgical intensive medical intervention (IMI), adjustable gastric band (BAND) or Roux-en-Y gastric bypass (RYGB) (n = 25 each). Changes in fasting plasma glucose (FPG) and glycated hemoglobin (HbA1c) were measured at 1-year after intervention. DNAm was quantified by Illumina 450 K arrays in baseline peripheral blood DNA. Epigenome-wide association studies were performed to identify CpG probes that modify the effects of different weight-loss interventions on glycemic outcomes, i.e., changes in FPG and HbA1c, by including an interaction term between types of intervention and DNAm. Models were adjusted for weight loss and baseline clinical factors.

Results: Baseline DNAm levels at 3216 and 117 CpGs were differentially associated with changes in FPG and HbA1c, respectively, when comparing RYGB versus IMI. Of these, 79 CpGs were significant for both FPG and HbA1c. The identified genes are enriched in adaptive thermogenesis, temperature homeostasis and regulation of cell population proliferation. Additionally, DNAm at 6 CpGs was differentially associated with changes in HbA1c when comparing RYGB versus BAND.

Conclusions: Baseline DNAm is differentially associated with glycemic outcomes in response to different types of weight-loss interventions, independent of weight loss and other clinical factors. Such findings provided initial evidence that baseline DNAm levels may serve as potential biomarkers predictive of differential glycemic outcomes in response to different types of weight-loss interventions.

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DNA甲基化与不同类型的减肥干预的血糖结果有不同的相关性:一项表观基因组范围的关联研究。
背景:据报道,DNA甲基化(DNAm)的改变是减肥手术导致代谢显著改善的一种机制。先前的研究主要集中在减肥干预后DNAm的变化,但干预前的DNAm是否可以解释血糖结果的可变性尚未得到研究。在这里,我们的目的是检查基线DNAm是否与不同类型的减肥干预措施诱导的血糖结果有不同的相关性。方法:参与者是75名患有严重肥胖的成年人,他们接受了非手术强化医疗干预(IMI)、可调节胃束带(band)或Roux-en-Y胃旁路术(RYGB)(n = 每个25个)。干预后1年测量空腹血糖(FPG)和糖化血红蛋白(HbA1c)的变化。DNAm通过Illumina 450K阵列在基线外周血DNA中进行定量。进行了全表观基因组关联研究,以确定CpG探针,通过包括干预类型和DNAm之间的相互作用项,来改变不同减肥干预对血糖结果的影响,即FPG和HbA1c的变化。模型根据体重减轻和基线临床因素进行了调整。结果:当比较RYGB和IMI时,3216和117CpG的基线DNAm水平分别与FPG和HbA1c的变化有差异。其中,79个CpG对FPG和HbA1c均具有显著性。所鉴定的基因在适应性产热、温度稳态和细胞群体增殖调节方面富集。此外,在比较RYGB和BAND时,6个CpG的DNAm与HbA1c的变化有不同的相关性。结论:基线DNAm与不同类型的减肥干预措施的血糖结果有不同的关联,与减肥和其他临床因素无关。这些发现提供了初步证据,表明基线DNAm水平可以作为潜在的生物标志物,预测对不同类型的减肥干预的不同血糖结果。
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来源期刊
Clinical Epigenetics
Clinical Epigenetics Biochemistry, Genetics and Molecular Biology-Developmental Biology
CiteScore
8.90
自引率
5.30%
发文量
150
审稿时长
12 weeks
期刊介绍: Clinical Epigenetics, the official journal of the Clinical Epigenetics Society, is an open access, peer-reviewed journal that encompasses all aspects of epigenetic principles and mechanisms in relation to human disease, diagnosis and therapy. Clinical trials and research in disease model organisms are particularly welcome.
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