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外周血细胞与口腔黏膜样本中与超重相关的基因甲基化平行关系。

Gene methylation parallelisms between peripheral blood cells and oral mucosa samples in relation to overweight.

作者信息

San-Cristobal Rodrigo, Navas-Carretero Santiago, Milagro Fermín I, Riezu-Boj J Ignacio, Guruceaga Elizabeth, Celis-Morales Carlos, Livingstone Katherine M, Brennan Lorraine, Lovegrove Julie A, Daniel Hannelore, Saris Wim H, Traczyk Iwonna, Manios Yannis, Gibney Eileen R, Gibney Michael J, Mathers John C, Martinez J Alfredo

机构信息

Department of Nutrition, Food Science and Physiology, Centre for Nutrition Research, University of Navarra, Pamplona, Spain.

CIBER Fisiopatología Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III, Madrid, Spain.

出版信息

J Physiol Biochem. 2016 Aug;73(3):465-474. doi: 10.1007/s13105-017-0560-6. Epub 2017 Mar 28.

Abstract

Epigenetics has an important role in the regulation of metabolic adaptation to environmental modifications. In this sense, the determination of epigenetic changes in non-invasive samples during the development of metabolic diseases could play an important role in the procedures in primary healthcare practice. To help translate the knowledge of epigenetics to public health practice, the present study aims to explore the parallelism of methylation levels between white blood cells and buccal samples in relation to obesity and associated disorders. Blood and buccal swap samples were collected from a subsample of the Spanish cohort of the Food4Me study. Infinium HumanMethylation450 DNA Analysis was carried out for the determination of methylation levels. Standard deviation for β values method and concordance correlation analysis were used to select those CpG which showed best parallelism between samples. A total of 277 CpGs met the criteria and were selected for an enrichment analysis and a correlation analysis with anthropometrical and clinical parameters. From those selected CpGs, four presented high associations with BMI (cg01055691 in GAP43; r = -0.92 and rho = -0.84 for blood; r = -0.89 and rho = -0.83 for buccal sample), HOMA-IR (cg00095677 in ATP2A3; r = 0.82 and rho = -0.84 for blood; r = -0.8 and rho = -0.83 for buccal sample) and leptin (cg14464133 in ADARB2; r = -0.9182 and rho = -0.94 for blood; r = -0.893 and rho = -0.79 for buccal sample). These findings demonstrate the potential application of non-invasive buccal samples in the identification of surrogate epigenetic biomarkers and identify methylation sites in GAP43, ATP2A3 and ADARB2 genes as potential targets in relation to overweight management and insulin sensibility.

摘要

表观遗传学在调节对环境变化的代谢适应方面发挥着重要作用。从这个意义上讲,在代谢性疾病发展过程中确定非侵入性样本中的表观遗传变化可能在初级医疗保健实践程序中发挥重要作用。为了帮助将表观遗传学知识转化为公共卫生实践,本研究旨在探讨白细胞和口腔样本中甲基化水平与肥胖及相关疾病之间的平行关系。从Food4Me研究的西班牙队列子样本中收集血液和口腔拭子样本。采用Infinium HumanMethylation450 DNA分析来确定甲基化水平。使用β值方法的标准差和一致性相关性分析来选择在样本之间显示出最佳平行关系的那些CpG。共有277个CpG符合标准,并被选用于富集分析以及与人体测量和临床参数的相关性分析。从那些选定的CpG中,有四个与体重指数(GAP43中的cg01055691;血液样本中r = -0.92,rho = -0.84;口腔样本中r = -0.89,rho = -0.83)、胰岛素抵抗指数(ATP2A3中的cg00095677;血液样本中r = 0.82,rho = -0.84;口腔样本中r = -0.8,rho = -0.83)和瘦素(ADARB2中的cg14464133;血液样本中r = -0.9182,rho = -0.94;口腔样本中r = -0.893,rho = -0.79)呈现高度相关性。这些发现证明了非侵入性口腔样本在识别替代表观遗传生物标志物方面的潜在应用,并确定了GAP43、ATP2A3和ADARB2基因中的甲基化位点作为与超重管理和胰岛素敏感性相关的潜在靶点。

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