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Epigenetic Markers of Renal Function in African Americans

机译:非洲裔美国人肾功能的表观遗传标记

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摘要

Chronic kidney disease (CKD) is an increasing concern in the United States due to its rapidly rising prevalence, particularly among African Americans. Epigenetic DNA methylation markers are becoming important biomarkers of chronic diseases such as CKD. To better understand how these methylation markers play a role in kidney function, we measured 26,428 DNA methylation sites in 972 African Americans from the Genetic Epidemiology Network of Arteriopathy (GENOA) study. We then evaluated (1) whether epigenetic markers are associated with estimated glomerular filtration rate (eGFR), (2) whether the significantly associated markers are also associated with traditional risk factors and/or novel biomarkers for eGFR, and (3) how much additional variation in eGFR is explained by epigenetic markers beyond established risk factors and biomarkers. The majority of methylation markers most significantly associated with eGFR (24 out of the top 30) appeared to function, at least in part, through pathways related to aging, inflammation, or cholesterol. However, six epigenetic markers were still able to significantly predict eGFR after adjustment for other risk factors. This work shows that epigenetic markers may offer valuable new insight into the complex pathophysiology of CKD in African Americans.
机译:由于慢性肾病(CKD)的患病率迅速上升,在美国尤其受到非裔美国人的关注,这一问题日益引起人们的关注。表观遗传的DNA甲基化标志物正成为慢性疾病如CKD的重要生物标志物。为了更好地了解这些甲基化标记物如何在肾脏功能中发挥作用,我们从“遗传性动脉病遗传流行病学网络”(GENOA)研究中测量了972个非洲裔美国人中的26,428个DNA甲基化位点。然后,我们评估了(1)表观遗传标记是否与估计的肾小球滤过率(eGFR)相关;(2)显着相关的标记是否还与eGFR的传统危险因素和/或新型生物标记相关;以及(3)另外多少表观遗传标记解释了eGFR的变异,超越了既定的危险因素和生物标记。与eGFR最显着相关的大多数甲基化标记(前30名中的24种)似乎至少部分地通过与衰老,炎症或胆固醇相关的途径起作用。然而,在调整其他危险因素后,六个表观遗传标记仍能够显着预测eGFR。这项工作表明,表观遗传标记可能为非洲裔美国人中CKD的复杂病理生理学提供有价值的新见解。

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