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 analyzed in buffy coat through a methylation array at baseline. DMRs were analyzed 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 analyze 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。这项研究的目的是确定肥胖受试者中的DMR，这些DMR可以预测减肥饮食干预的反应及其与代谢变量的关系。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分位数：反应者（R; n = 64）和非反应者（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（芯片分析甲基化管线）功能分析DMR。在R和NR之间进行的基线DNA甲基化分析显示，DMR位于对氧磷酶3基因（PON3）上，由13个CpG位点组成，其中11个在R中显着超甲基化。作为DMR甲基化的量度。分析表明PON3之间存在相关性DNA甲基化和BMI丢失。该z值与PON3蛋白血清水平负相关。两组之间血清总对氧磷酶活性无差异，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，该DMR与血清中PON3蛋白水平有关，可以用作预测对减肥饮食干预措施反应的潜在生物标记。