In:
AIDS, Ovid Technologies (Wolters Kluwer Health), Vol. 36, No. 11 ( 2022-09-01), p. 1563-1571
Abstract:
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 , IFITM 1, 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.
Type of Medium:
Online Resource
ISSN:
0269-9370
,
1473-5571
DOI:
10.1097/QAD.0000000000003279
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2022
detail.hit.zdb_id:
2012212-3
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