Soluble CD14-associated DNA methylation sites predict mortality among men with HIV infection
Year: 2022
Type: review
Abstract: OBJECTIVES: Elevated plasma levels of sCD14 predict all-cause mortality in people with HIV (PWH). Epigenetic regulation plays a key role in infection and inflammation. To reveal the epigenetic relationships between sCD14, immune function and disease progression among PWH, we conducted an epigenome-wide association study (EWAS) of sCD14 and investigated the relationship with mortality. DESIGN AND METHODS: DNA methylation (DNAm) levels of peripheral blood samples from PWH in the Veterans Aging Cohort Study (VACS) were measured using the Illumina Infinium Methylation 450K (n = 549) and EPIC (850K) BeadChip (n = 526). Adjusted for covariates and multiple testing, we conducted an epigenome-wide discovery, replication, and meta-analysis to identify significant associations with sCD14. We then examined and replicated the relationship between the principal epigenetic sites and survival using Cox regression models. FINDINGS: We identified 118 DNAm sites significantly associated with sCD14 in the meta-analysis of 1075 PWH. The principal associated DNAm sites mapped to genes (e.g. STAT1, PARP9, IFITM1, MX1, and IFIT1) related to inflammation and antiviral response. Adjusting for multiple testing, 10 of 118 sCD14-associated DNAm sites significantly predicted survival time conditional on sCD14 levels. CONCLUSION: The identification of DNAm sites independently predicting survival may improve our understanding of prognosis and potential therapeutic targets among PWH.
Source: AIDS
Language: English
Topic: HIV Research and Treatment
Subfield: Virology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
Funders: National Institutes of Health, National Institute on Alcohol Abuse and Alcoholism, National Heart, Lung, and Blood Institute, National Institute of Mental Health, National Institute on Drug Abuse, National Institute of Allergy and Infectious Diseases, National Institute of Diabetes and Digestive and Kidney Diseases, National Center for Advancing Translational Sciences
Awards: Multi-omic Predictors of Renal Function among HIV-infected Individuals of African Ancestry, Feature selection of DNA methylation biosignatures for neuropathy with comorbid drug abuse in the setting of HIV infection, 2/6 COMpAAAS U01: Observation Study, Defining the impact of injection drug use on antiretroviral therapy and HIV treatment outcomes: an (epi)genomic approach, Alcohol Associated Outcomes Among HIV+/- Aging Veterans, 1/6 COMpAAAS U24: Coordinating Center, Novel Mechanisms Driving Excess Atherosclerotic Cardiovascular Disease Risk in the Context of HIV: The Role of Liver Injury, Methylome-wide and mQTL analysis of HIV progression in the context of cocaine use, Phase II study to evaluate the efficacy and safety of baricitinib for reduction of HIV in the central nervous system, Center for AIDS Research at Emory University, Yale Clinical and Translational Science Award, Emory National Primate Research Center
OpenAlex ID: W4292241818