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低氧耗量与肥胖合并睡眠呼吸暂停低通气综合征患者 IL-6 的低甲基化和分泌增加有关。

Low Oxygen Consumption is Related to a Hypomethylation and an Increased Secretion of IL-6 in Obese Subjects with Sleep Apnea-Hypopnea Syndrome.

机构信息

University of Navarra, Department of Nutrition, Food Science and Physiology, School of Pharmacy and Nutrition, Pamplona, Spain.

出版信息

Ann Nutr Metab. 2017;71(1-2):16-25. doi: 10.1159/000478276. Epub 2017 Jul 4.

DOI:10.1159/000478276
PMID:28675894
Abstract

BACKGROUND

Deoxyribonucleic acid (DNA) methylation is an epigenetic modification involved in gene expression regulation, usually via gene silencing, which contributes to the risks of many multifactorial diseases. The aim of the present study was to analyze the influence of resting oxygen consumption on global and gene DNA methylation as well as protein secretion of inflammatory markers in blood cells from obese subjects with sleep apnea-hypopnea syndrome (SAHS).

METHODS

A total of 44 obese participants with SAHS were categorized in 2 groups according to their resting oxygen consumption. DNA methylation levels were evaluated using a methylation-sensitive high resolution melting approach.

RESULTS

The analyzed interleukin 6 (IL6) gene cytosine phosphate guanine (CpG) islands showed a hypomethylation, while serum IL-6 was higher in the low compared to the high oxygen consumption group (p < 0.05). Moreover, an age-related loss of DNA methylation of tumor necrosis factor (B = -0.82, 95% CI -1.33 to -0.30) and long interspersed nucleotide element 1 (B = -0.46; 95% CI -0.87 to -0.04) gene CpGs were found. Finally, studied CpG methylation levels of serpin peptidase inhibitor, clade E member 1 (r = 0.43; p = 0.01), and IL6 (r = 0.41; p = 0.02) were positively associated with fat-free mass.

CONCLUSIONS

These findings suggest a potential role of oxygen in the regulation of inflammatory genes. Oxygen consumption measurement at rest could be proposed as a clinical biomarker of metabolic health.

摘要

背景

脱氧核糖核酸(DNA)甲基化是一种参与基因表达调控的表观遗传修饰,通常通过基因沉默来实现,这导致了许多多因素疾病的发生风险。本研究旨在分析静息耗氧量对肥胖合并睡眠呼吸暂停低通气综合征(SAHS)患者血细胞中炎症标志物的整体和基因 DNA 甲基化以及蛋白质分泌的影响。

方法

根据静息耗氧量,将 44 名肥胖合并 SAHS 的患者分为两组。采用甲基化敏感高分辨率熔解曲线分析评估 DNA 甲基化水平。

结果

分析的白细胞介素 6(IL6)基因胞嘧啶磷酸鸟嘌呤(CpG)岛呈低甲基化状态,而低氧消耗组的血清 IL-6 高于高氧消耗组(p<0.05)。此外,还发现肿瘤坏死因子(B=-0.82,95%CI-1.33 至-0.30)和长散布核元件 1(B=-0.46;95%CI-0.87 至-0.04)基因 CpG 的年龄相关 DNA 甲基化丢失。最后,研究发现丝氨酸蛋白酶抑制剂、E 族成员 1(r=0.43;p=0.01)和 IL6(r=0.41;p=0.02)的 CpG 甲基化水平与去脂体重呈正相关。

结论

这些发现表明氧在调节炎症基因方面可能具有潜在作用。静息耗氧量的测量可以作为代谢健康的临床生物标志物。

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