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年轻非裔美国人中与围产期获得性 HIV 相关的表观遗传学年龄。

Epigenetic Age in Young African American Adults With Perinatally Acquired HIV.

机构信息

Department of Biostatistics and Epidemiology, Rutgers School of Public Health, Piscataway, NJ.

Department of Medicine, College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, NY.

出版信息

J Acquir Immune Defic Syndr. 2021 Aug 1;87(4):1102-1109. doi: 10.1097/QAI.0000000000002687.

Abstract

BACKGROUND

Prior studies have measured accelerated aging in people with HIV using a DNA methylation (DNAm)-based biomarker of aging, "epigenetic age," but data are limited in African American (AA) young adults with perinatally acquired HIV infection (PHIV).

METHODS

We performed a cross-sectional study of AA young adults aged 20-35 years with PHIV (N = 31) and seronegative controls (N = 30) using DNAm measured in whole blood and cognitive function measured by the NIH Toolbox. Illumina EPIC array was used to measure DNAm age and accelerated aging markers including epigenetic age acceleration (EAA), as well as extrinsic (EEAA) and intrinsic (IEAA) EAA.

RESULTS

PHIV and controls did not differ by sex (45 vs. 43% male), chronological age (26.2 vs. 28.0 years), or ethnicity. Chronological age and DNAm age were correlated (r = 0.56, P < 0.01). PHIV had a higher mean EAA (2.86 ± 6.5 vs. -2.96 ± 3.9, P < 0.01) and EEAA (4.57 ± 13.0 vs. -4.72 ± 6.0, P < 0.01) than controls; however, IEAA was not different between groups. Among PHIV, EAA and EEAA were higher in those with HIV viral load ≥50 copies/mL than <50 copies/mL (EEA: 8.1 ± 5.2 vs. 0.11 ± 5.5, P = 0 < 0.01 and EEAA: 16.1 ± 10.6 vs. -1.83 ± 9.7, P < 0.01). We observed negative correlations (r = -0.36 to -0.31) between EEAA and executive function, attention, and language scores.

CONCLUSIONS

In conclusion, EAA in blood was observed in AA young adults with PHIV on ART using 2 measures, including EEAA which upweights the contribution of immunosenescent cell types. However, there was no evidence of age acceleration with a measure independent of cell type composition.

摘要

背景

先前的研究使用基于 DNA 甲基化(DNAm)的衰老生物标志物“表观遗传年龄”来衡量 HIV 感染者的加速衰老,但针对通过母婴传播感染 HIV(PHIV)的非裔美国(AA)年轻成年人的数据有限。

方法

我们对 31 名年龄在 20-35 岁之间的 PHIV 年轻成年人(PHIV)和 30 名血清阴性对照(对照组)进行了横断面研究,使用全血中的 DNAm 和 NIH 工具包测量的认知功能。Illumina EPIC 阵列用于测量 DNAm 年龄和加速衰老标志物,包括表观遗传年龄加速(EAA)、外在(EEAA)和内在(IEAA)EAA。

结果

PHIV 和对照组在性别(45%对 43%男性)、实际年龄(26.2 对 28.0 岁)和种族方面没有差异。实际年龄和 DNAm 年龄呈正相关(r = 0.56,P < 0.01)。PHIV 的平均 EAA(2.86 ± 6.5 对 -2.96 ± 3.9,P < 0.01)和 EEAA(4.57 ± 13.0 对 -4.72 ± 6.0,P < 0.01)均高于对照组,但两组之间的 IEAA 没有差异。在 PHIV 中,HIV 病毒载量≥50 拷贝/mL 的患者的 EAA 和 EEAA 高于<50 拷贝/mL 的患者(EEA:8.1 ± 5.2 对 0.11 ± 5.5,P = 0 < 0.01;EEAA:16.1 ± 10.6 对 -1.83 ± 9.7,P < 0.01)。我们观察到 EEAA 与执行功能、注意力和语言评分呈负相关(r = -0.36 至 -0.31)。

结论

总之,在使用 2 种测量方法的接受 ART 治疗的 AA 年轻 PHIV 成年人中观察到血液中的 EAA,包括对免疫衰老细胞类型权重更大的 EEAA。然而,没有证据表明细胞类型组成独立的测量存在衰老加速。

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