ABSTRACT

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.

摘要

差异甲基化区域 (DMR) 是具有不同甲基化状态的基因组区域。本研究的目的是确定肥胖受试者的 DMR，这些 DMR 可预测对减肥饮食干预的反应及其与代谢变量的关联。根据体重指数 (BMI) 的变化，根据对低热量饮食的反应，将 201 名超重和肥胖的受试者分为三组：反应者 (R; n = 64) 和无反应者 (NR; n = 63) . R 组损失 4.55 ± 0.91 BMI 单位 (kg/m ² )，NR 组损失 1.95 ± 0.73 kg/m ²(p < 0.001)。通过基线处的甲基化阵列分析血沉棕黄层中的 DNA 甲基化。使用 R 软件中的 ChAMP（芯片分析甲基化管道）功能分析 DMR。R 和 NR 之间的基线 DNA 甲基化分析显示，DMR 位于对氧磷酶 3 基因 ( PON3 )，由 13 个 CpG 位点组成，其中 11 个在 R 中显着高甲基化。为了分析这 11 个 CpG 对体重减轻的影响，z 分数是作为 DMR 甲基化的量度进行。该分析显示PON3之间存在相关性DNA甲基化和BMI损失。该 z 分数与 PON3 蛋白血清水平呈负相关。血清中总对氧磷酶活性在各组之间没有差异，但 PON 酶活性与氧化 LDL 水平呈正相关。本研究确定了PON3基因内的 DMR，它与血清中 PON3 蛋白水平相关，可用作预测对减肥饮食干预反应的潜在生物标志物。