Sun Yan V, Lazarus Alicia, Smith Jennifer A, Chuang Yu-Hsuan, Zhao Wei, Turner Stephen T, Kardia Sharon L R
Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia, United States of America.
PLoS One. 2013 Aug 19;8(8):e73480. doi: 10.1371/journal.pone.0073480. eCollection 2013.
A more thorough understanding of the differences in DNA methylation (DNAm) profiles in populations may hold promise for identifying molecular mechanisms through which genetic and environmental factors jointly contribute to human diseases. Inflammation is a key molecular mechanism underlying several chronic diseases including cardiovascular disease, and it affects DNAm profile on both global and locus-specific levels. To understand the impact of inflammation on the DNAm of the human genome, we investigated DNAm profiles of peripheral blood leukocytes from 966 African American participants in the Genetic Epidemiology Network of Arteriopathy (GENOA) study. By testing the association of DNAm sites on CpG islands of over 14,000 genes with C-reactive protein (CRP), an inflammatory biomarker of cardiovascular disease, we identified 257 DNAm sites in 240 genes significantly associated with serum levels of CRP adjusted for age, sex, body mass index and smoking status, and corrected for multiple testing. Of the significantly associated DNAm sites, 80.5% were hypomethylated with higher CRP levels. The most significant Gene Ontology terms enriched in the genes associated with the CRP levels were immune system process, immune response, defense response, response to stimulus, and response to stress, which are all linked to the functions of leukocytes. While the CRP-associated DNAm may be cell-type specific, understanding the DNAm association with CRP in peripheral blood leukocytes of multi-ethnic populations can assist in unveiling the molecular mechanism of how the process of inflammation affects the risks of developing common disease through epigenetic modifications.
更全面地了解人群中DNA甲基化（DNAm）谱的差异，可能有助于识别遗传和环境因素共同导致人类疾病的分子机制。炎症是包括心血管疾病在内的几种慢性疾病的关键分子机制，它在整体和基因座特异性水平上影响DNAm谱。为了了解炎症对人类基因组DNAm的影响，我们调查了动脉病遗传流行病学网络（GENOA）研究中966名非裔美国参与者外周血白细胞的DNAm谱。通过测试超过14000个基因的CpG岛上的DNAm位点与C反应蛋白（CRP）（一种心血管疾病的炎症生物标志物）的关联，我们在240个基因中鉴定出257个DNAm位点，这些位点与校正了年龄、性别、体重指数和吸烟状况并经过多重检验校正后的血清CRP水平显著相关。在显著相关的DNAm位点中，80.5%在CRP水平较高时发生低甲基化。与CRP水平相关的基因中最显著富集的基因本体学术语是免疫系统过程、免疫反应、防御反应、对刺激的反应和对应激的反应，这些都与白细胞的功能相关。虽然与CRP相关的DNAm可能具有细胞类型特异性，但了解多民族人群外周血白细胞中DNAm与CRP的关联有助于揭示炎症过程如何通过表观遗传修饰影响常见疾病发生风险的分子机制。
