PDF(Pubmed)
Abstract：
BACKGROUND: DNA methylation may be a link between HIV, aging, and the increased risk of lung comorbidities. We investigated whether bronchoalveolar lavage (BAL) cells of people living with HIV (PLWH) demonstrate epigenetic disruptions and advanced epigenetic aging.
METHODS: BAL cell DNA methylation from 25 PLWH and 16 HIV-uninfected individuals were tested for differential methylation of Alu and LINE-1 sites, markers of aging. We used a weighted gene correlation network analysis to identify HIV- and age-associated co-methylation networks. We tested the effect of HIV on DNA methylation using a robust linear model (false discovery rate < 0.10).
RESULTS: The BAL cells of PLWH were marked by global hypomethylation in both Alu and LINE-1 elements. Six co-methylated CpG networks were identified that were significantly associated with age; of these, the red module was significantly differentially methylated in PLWH and enriched pathways (e.g., Ras signaling and T-cell receptors). We identified 6428 CpG sites associated with HIV.
CONCLUSIONS: We have shown here for the first time that alterations in the DNA methylation of BAL cells in the lung with HIV show a pattern of advanced aging. This study strongly supports that HIV may contribute to an increased the risk of lung comorbidities through the epigenetics of aging.
METHODS: BAL cell DNA methylation from 25 PLWH and 16 HIV-uninfected individuals were tested for differential methylation of Alu and LINE-1 sites, markers of aging. We used a weighted gene correlation network analysis to identify HIV- and age-associated co-methylation networks. We tested the effect of HIV on DNA methylation using a robust linear model (false discovery rate < 0.10).
RESULTS: The BAL cells of PLWH were marked by global hypomethylation in both Alu and LINE-1 elements. Six co-methylated CpG networks were identified that were significantly associated with age; of these, the red module was significantly differentially methylated in PLWH and enriched pathways (e.g., Ras signaling and T-cell receptors). We identified 6428 CpG sites associated with HIV.
CONCLUSIONS: We have shown here for the first time that alterations in the DNA methylation of BAL cells in the lung with HIV show a pattern of advanced aging. This study strongly supports that HIV may contribute to an increased the risk of lung comorbidities through the epigenetics of aging.
摘要：
背景：DNA甲基化可能是HIV之间的联系，老化，以及肺部合并症的风险增加。我们调查了HIV（PLWH）感染者的支气管肺泡灌洗（BAL）细胞是否表现出表观遗传破坏和晚期表观遗传衰老。
方法：检测来自25个PLWH和16个未感染HIV的个体的BAL细胞DNA甲基化的Alu和LINE-1位点的差异甲基化，衰老的标志。我们使用加权基因相关网络分析来鉴定HIV和年龄相关的共甲基化网络。我们使用稳健的线性模型（错误发现率<0.10）测试了HIV对DNA甲基化的影响。
结果：PLWH的BAL细胞在Alu和LINE-1元件中都被整体低甲基化标记。确定了六个与年龄显着相关的共甲基化CpG网络；其中，红色模块在PLWH和富集途径中显著差异甲基化(例如，Ras信号传导和T细胞受体）。我们确定了与HIV相关的6428个CpG位点。
结论：我们在此首次表明，感染HIV的肺中BAL细胞DNA甲基化的改变显示出一种晚期衰老的模式。这项研究强烈支持HIV可能通过衰老的表观遗传学导致肺部合并症的风险增加。
方法：检测来自25个PLWH和16个未感染HIV的个体的BAL细胞DNA甲基化的Alu和LINE-1位点的差异甲基化，衰老的标志。我们使用加权基因相关网络分析来鉴定HIV和年龄相关的共甲基化网络。我们使用稳健的线性模型（错误发现率<0.10）测试了HIV对DNA甲基化的影响。
结果：PLWH的BAL细胞在Alu和LINE-1元件中都被整体低甲基化标记。确定了六个与年龄显着相关的共甲基化CpG网络；其中，红色模块在PLWH和富集途径中显著差异甲基化(例如，Ras信号传导和T细胞受体）。我们确定了与HIV相关的6428个CpG位点。
结论：我们在此首次表明，感染HIV的肺中BAL细胞DNA甲基化的改变显示出一种晚期衰老的模式。这项研究强烈支持HIV可能通过衰老的表观遗传学导致肺部合并症的风险增加。
