Chen Junyu, Hui Qin, Wang Zeyuan, Wilson Francis P, So-Armah Kaku, Freiberg Matthew S, Justice Amy C, Xu Ke, Zhao Wei, Ammous Farah, Smith Jennifer A, Kardia Sharon L R, Gwinn Marta, Marconi Vincent C, Sun Yan V
Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia, USA.
Department of Medicine, Yale University School of Medicine, Connecticut, USA.
Kidney Int Rep. 2023 Mar 2;8(5):1076-1086. doi: 10.1016/j.ekir.2023.02.1085. eCollection 2023 May.
People with HIV (PWH) of African ancestry have faster decline of kidney function and faster progression to end-stage renal disease than PWH of European ancestry. DNA methylation have been associated with kidney function in the general population, however, their relationships are unclear for PWH of African ancestry.
We performed epigenome-wide association studies (EWAS) of estimated glomerular filtration rate (eGFR) among PWH of African ancestry in 2 subsets of the Veterans Aging Cohort Study cohort ( = 885), followed by a meta-analysis to combine the results. Replication was conducted among independent African American samples without HIV.
DNA methylation sites cg17944885 near Zinc Finger Family Member 788 () and Zinc Finger Protein 20 (), and cg06930757 in were significantly associated with eGFR among PWH of African ancestry (false discovery rate < 0.05). DNA methylation site cg17944885 was also associated with eGFR among different populations including African Americans without HIV.
Our study attempted to address an important gap in the literature and to understand the role of DNA methylation in renal diseases in PWH of African ancestry. Replication of cg17944885 among different populations suggests there may be a common pathway for renal diseases progression among PWH and people without HIV, and across different ancestral groups. Our results suggest that genes and could be involved in a pathway linking DNA methylation to renal diseases among PWH and are worth further investigation.
与欧洲血统的艾滋病毒感染者相比，非洲血统的艾滋病毒感染者（PWH）肾功能下降更快，向终末期肾病进展更快。在普通人群中，DNA甲基化与肾功能有关，然而，对于非洲血统的PWH，它们之间的关系尚不清楚。
我们在退伍军人老龄化队列研究队列的2个亚组（n = 885）中，对非洲血统的PWH进行了估计肾小球滤过率（eGFR）的全表观基因组关联研究（EWAS），随后进行荟萃分析以合并结果。在无艾滋病毒的独立非裔美国人样本中进行重复验证。
锌指家族成员788（ZNF788）和锌指蛋白20（ZNF20）附近的DNA甲基化位点cg17944885，以及ZNF20中的cg06930757与非洲血统的PWH中的eGFR显著相关（错误发现率<0.05）。DNA甲基化位点cg17944885在包括无艾滋病毒的非裔美国人在内的不同人群中也与eGFR相关。
我们的研究试图填补文献中的一个重要空白，并了解DNA甲基化在非洲血统的PWH肾脏疾病中的作用。cg17944885在不同人群中的重复验证表明，PWH和无艾滋病毒的人以及不同祖先群体之间可能存在肾脏疾病进展的共同途径。我们的结果表明，ZNF788和ZNF20基因可能参与了一条将DNA甲基化与PWH肾脏疾病联系起来的途径，值得进一步研究。
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