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Inflammation-related genes are associated with epigenetic aging in HIV.

ABSTRACT: 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-? -?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-? 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.

SUBMITTER: Sundermann EE

PROVIDER: S-EPMC6923602 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Inflammation-related genes are associated with epigenetic aging in HIV.

Sundermann Erin E EE Hussain Mariam A MA Moore David J DJ Horvath Steven S Lin David T S DTS Kobor Michael S MS Levine Andrew A

Journal of neurovirology 20190708 6

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 p ...[more]

PMID: 31286441

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Project description:BACKGROUND:Chronic obstructive pulmonary disease (COPD) is a chronic lung inflammatory disease which has a close relationship with aging. Genome-wide analysis reveals that DNA methylation markers vary obviously with age. DNA methylation variations in peripheral blood have the potential to be biomarkers for COPD. However, the specific DNA methylation of aging-related genes in the peripheral blood of COPD patients remains largely unknown. METHODS:Firstly, 9 aging-related differentially expressed genes (DEGs) in COPD patients were screened out from the 25 aging-related genes profile through a comprehensive screening strategy. Secondly, qPCR and multiple targeted bisulfite enrichment sequencing (MethTarget) were used to detect the mRNA level and DNA methylation level of the 9 differentially expressed genes in the peripheral blood of 60 control subjects and 45 COPD patients. The candidate functional CpG sites were selected on the basis of the regulation ability of the target gene expression. Thirdly, the correlation was evaluated between the DNA methylation level of the key CpG sites and the clinical parameters of COPD patients, including forced expiratory volume in one second (FEV1), forced expiratory volume in one second as percentage of predicted volume (FEV1%), forced expiratory volume/ forced vital capacity (FEV/FVC), modified British medical research council (mMRC) score, acute exacerbation frequency and the situation of frequent of acute aggravation (CAT) score. Lastly, differentially methylated CpG sites unrelated to smoking were also determined in COPD patients. RESULTS:Of the 9 differentially expressed aging-related genes, the mRNA expression of 8 genes were detected to be significantly down-regulated in COPD group, compared with control group. Meanwhile, the methylated level of all aging-related genes was changed in COPD group containing 219 COPD-related CpG sites in total. Notably, 27 CpG sites of FOXO3 gene showed a lower False Discovery Rate (FDR) and higher methylation difference values. Also, some variable DNA methylation is associated with the severity of COPD. Additionally, of the 219 COPD-related CpG sites, 147 CpG sites were not related to smoking. CONCLUSION:These results identified that the mRNA expression and DNA methylation level of aging-related genes were changed in male COPD patients, which provides a molecular link between aging and COPD. The identified CpG markers are associated with the severity of COPD and provide new insights into the prediction and identification of COPD.

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Inflammation-related genes are associated with epigenetic aging in HIV.

Publications

Inflammation-related genes are associated with epigenetic aging in HIV.

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