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Epigenetic silencing of the ANKRD26 gene correlates to the pro-inflammatory profile and increased cardio-metabolic risk factors in human obesity.
Clinical Epigenetics ( IF 5.7 ) Pub Date : 2019-12-04 , DOI: 10.1186/s13148-019-0768-0
Antonella Desiderio 1, 2 , Michele Longo 1, 2 , Luca Parrillo 1, 2 , Michele Campitelli 1, 2 , Giuseppe Cacace 1, 2 , Sonia de Simone 1, 2 , Rosa Spinelli 1, 2 , Federica Zatterale 1, 2 , Serena Cabaro 1, 2 , Pasquale Dolce 3 , Pietro Formisano 1, 2 , Marco Milone 4 , Claudia Miele 1, 2 , Francesco Beguinot 1, 2 , Gregory A Raciti 1, 2
Affiliation  

BACKGROUND Obesity is a major worldwide threat to human health. Increasing evidence indicates that epigenetic modifications have a major impact on the natural history of this disorder. Ankyrin Repeat Domain 26 (Ankrd26) is involved in the development of both obesity and diabetes in mice and is modulated by environmentally induced epigenetic modifications. This study aims at investigating whether impaired ANKRD26 gene expression and methylation occur in human obesity and whether they correlate to the phenotype of these subjects. RESULTS We found that downregulation of ANKRD26 mRNA and hyper-methylation of a specific region of the ANKRD26 promoter, embedding the CpG dinucleotides - 689, - 659, and - 651 bp, occur in peripheral blood leukocytes from obese compared with the lean subjects. ANKRD26 gene expression correlates inversely to the percentage of DNA methylation at these 3 CpG sites. Luciferase assays reveal a cause-effect relationship between DNA methylation at the 3 CpG sites and ANKRD26 gene expression. Finally, both ANKRD26 mRNA levels and CpG methylation correlate to body mass index and to the pro-inflammatory status and the increased cardio-metabolic risk factors of these same subjects. CONCLUSION Downregulation of the ANKRD26 gene and hyper-methylation at specific CpGs of its promoter are common abnormalities in obese patients. These changes correlate to the pro-inflammatory profile and the cardio-metabolic risk factors of the obese individuals, indicating that, in humans, they mark adverse health outcomes.

中文翻译:

ANKRD26基因的表观遗传沉默与人类肥胖中的促炎特征和增加的心脏代谢危险因素有关。

背景技术肥胖是全世界范围内对人类健康的主要威胁。越来越多的证据表明,表观遗传修饰对这种疾病的自然病程有重大影响。锚蛋白重复结构域26(Ankrd26)与小鼠肥胖和糖尿病的发展有关,并受环境诱导的表观遗传修饰的调节。这项研究旨在调查在人类肥胖症中是否发生受损的ANKRD26基因表达和甲基化,以及它们是否与这些受试者的表型相关。结果我们发现与瘦弱的受试者相比,肥胖的外周血白细胞中发生了ANKRD26 mRNA的下调和ANKRD26启动子特定区域的超甲基化,其中嵌入了CpG二核苷酸-689,-659和-651 bp。ANKRD26基因表达与这3个CpG位点的DNA甲基化百分比成反比。萤光素酶检测揭示了3个CpG位点的DNA甲基化与ANKRD26基因表达之间的因果关系。最后,ANKRD26 mRNA水平和CpG甲基化均与这些受试者的体重指数,促炎状态和增加的心血管代谢危险因素相关。结论ANKRD26基因的下调和其启动子的特定CpGs的高甲基化是肥胖患者的常见异常。这些变化与肥胖个体的促炎特征和心血管代谢危险因素相关,表明在人类中,它们标志着不利的健康结果。萤光素酶检测揭示了3个CpG位点的DNA甲基化与ANKRD26基因表达之间的因果关系。最后,ANKRD26 mRNA水平和CpG甲基化均与这些受试者的体重指数,促炎状态和增加的心血管代谢危险因素相关。结论ANKRD26基因的下调和其启动子的特定CpGs的高甲基化是肥胖患者的常见异常。这些变化与肥胖个体的促炎特征和心血管代谢危险因素相关,表明在人类中,它们标志着不利的健康结果。萤光素酶检测揭示了3个CpG位点的DNA甲基化与ANKRD26基因表达之间的因果关系。最后,ANKRD26 mRNA水平和CpG甲基化均与这些受试者的体重指数,促炎状态和增加的心血管代谢危险因素相关。结论ANKRD26基因的下调和其启动子的特定CpGs的高甲基化是肥胖患者的常见异常。这些变化与肥胖个体的促炎特征和心血管代谢危险因素相关,表明在人类中,它们标志着不利的健康结果。这些相同受试者的ANKRD26 mRNA水平和CpG甲基化均与体重指数,促炎状态和增加的心血管代谢危险因素相关。结论ANKRD26基因的下调和其启动子的特定CpGs的高甲基化是肥胖患者的常见异常。这些变化与肥胖个体的促炎特征和心血管代谢危险因素相关,表明在人类中,它们标志着不利的健康结果。这些相同受试者的ANKRD26 mRNA水平和CpG甲基化均与体重指数,促炎状态和增加的心血管代谢危险因素相关。结论ANKRD26基因的下调和其启动子的特定CpGs的高甲基化是肥胖患者的常见异常。这些变化与肥胖个体的促炎特征和心血管代谢危险因素相关,表明在人类中,它们标志着不利的健康结果。
更新日期:2019-12-04
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