Department of Psychiatry, University of California, San Diego, 9500 Gilman Dr, La Jolla, CA, 92093, USA.
San Diego State University/University of California San Diego Joint Doctoral Program in Clinical Psychology, 6363 Alvarado Ct, San Diego, CA, 92120, USA.
J Neurovirol. 2019 Dec;25(6):853-865. doi: 10.1007/s13365-019-00777-4. Epub 2019 Jul 8.
Chronic inflammation is characteristic of both HIV and aging ("inflammaging") and may contribute to the accelerated aging observed in people living with HIV (PLWH). We examined whether three inflammation-related single-nucleotide polymorphisms (SNPs) were risk factors for accelerated aging and HIV-associated, non-AIDS (HANA) conditions among PLWH. We examined 155 postmortem cases with HIV (mean age = 47.3, 81% male, 68% self-reported White) from the National NeuroAIDS Tissue Consortium who had pre-mortem neurobehavioral/medical/virologic data and epigenomic data from occipital cortex tissue. Accelerated aging was measured according to the Epigenetic Clock; an aging biomarker based on DNA methylation levels. Past or current age-associated HANA conditions including cerebrovascular, liver and kidney disease, chronic obstructive pulmonary disease, cancer, and diabetes were determined via self-report. Epigenetic Aging Z-scores and likelihood of past/current HANA conditions were compared between major allele homozygotes and minor allele carriers for each SNP (IL-6 - 174G>C, IL-10 - 592C>A, TNF-α - 308 G>A) separately. Analyses were adjusted for relevant demographic/clinical factors. Epigenetic aging (e.g., higher Z-scores) was significantly greater in IL-6 C allele carriers (p = .002) and IL-10 CC homozygotes (p = .02) compared to other genotype groups. The likelihood of any past/current HANA condition did not differ by IL-10 genotype but was 3.36 times greater in IL-6 C allele carriers versus others (OR = 3.36, 95%CI = 1.09-10.34, p = .03). TNF-α genotype was not associated with epigenetic aging or HANA conditions. IL-6 and IL-10 SNPs may help to identify PLWH who are at high risk for accelerated aging. These insights into pathophysiological pathways may inform interventional approaches to treat rapid aging among PLWH.
慢性炎症是 HIV 和衰老的特征（“炎症衰老”），可能导致 HIV 感染者（PLWH）中观察到的加速衰老。我们研究了三个与炎症相关的单核苷酸多态性（SNP）是否是 PLWH 加速衰老和与 HIV 相关的非艾滋病（HANA）疾病的危险因素。我们检查了来自国家神经艾滋病组织联盟的 155 例 HIV 死后病例（平均年龄为 47.3 岁，81%为男性，68%自我报告为白人），这些病例生前有神经行为学/医学/病毒学数据和枕叶皮质组织的表观基因组数据。根据基于 DNA 甲基化水平的衰老生物标志物——表观遗传时钟，衡量加速衰老的程度。通过自我报告确定过去或当前与年龄相关的 HANA 疾病，包括脑血管疾病、肝脏和肾脏疾病、慢性阻塞性肺疾病、癌症和糖尿病。分别比较每个 SNP（IL-6-174G>C、IL-10-592C>A、TNF-α-308G>A）的主要等位基因纯合子和次要等位基因携带者的表观遗传衰老 Z 分数和过去/当前 HANA 疾病的可能性。分析调整了相关的人口统计学/临床因素。与其他基因型组相比，IL-6 C 等位基因携带者（p=0.002）和 IL-10 CC 纯合子（p=0.02）的表观遗传衰老（例如，更高的 Z 分数）明显更大。IL-10 基因型与任何过去/当前 HANA 疾病的可能性无关，但与其他基因型相比，IL-6 C 等位基因携带者的可能性高 3.36 倍（OR=3.36，95%CI=1.09-10.34，p=0.03）。TNF-α 基因型与表观遗传衰老或 HANA 疾病无关。IL-6 和 IL-10 SNP 可能有助于识别加速衰老风险较高的 PLWH。这些对病理生理途径的见解可能为治疗 PLWH 快速衰老提供干预方法。
