Epigenetic Associations of Circulating Interleukin 6 among People with HIV Pubblico

Abstract

 

Background 

Interleukin-6 (IL-6), the proinflammatory cytokine, is a key signal transducer in response to the viral infection. Elevated plasma levels of IL-6 were associated with mortality in people with HIV (PWH). Inflammation and immune responses could be regulated by epigenetic modifications. An Epigenome-Wide Association study (EWAS) was conducted to investigate the epigenetic association with IL-6 among PWH. 

 

Method 

Peripheral blood samples from the Veterans Aging Cohort Study (VACS) participants were investigated for epigenome-wide DNA methylation (DNAm) levels using the Illumina Infinium Methylation 450K (n=512) and EPIC BeadChip (n=490). An epigenome-wide discovery, replication and meta-analysis were performed to identify the significant epigenetic associations with IL-6 using multiple regression models adjusted for covariates and batch effects.  

 

Results 

In the meta-analysis of 1,002 male veterans with HIV, 111 DNAm sites were significantly associated with IL-6 after correction for multiple testing. The identified IL-6-associated DNAm site were highly concordant between the 450K and EPIC sub-cohorts. The top IL-6- associated DNAm sites mapped to genes including VMP1, IFITM1, STAT1, and MX1, all related to innate immune responses and antiviral response.  

 

Discussion  

The key findings of the principal genes and the pathways epigenetically related to the IL-6 levels could help understand the chronic inflammation mechanisms of HIV infection. The robust findings of IL-6-assocaited DNAm sites may uncover potential therapeutic targets related to key pathways influencing the immune recovery and chronic disease outcomes among PWH. 

 

Conclusion

This EWAS summarized VMP1, IFITM1, STAT1, MX1 and OSA1 genes related to IL-6 methylation among PWH. Those DNAm sites are helpful to further investigate the pathogenesis of inflammation and can imply as a necessary accompaniment to study the chronic diseases and survival status of HIV infection.

Table of Contents

Table of Contents 

Introduction .......................................................................................................................... 1 

Methods ................................................................................................................................ 5 

Study sample .................................................................................................................................5 

DNA Methylation data processing and quality control ....................................................................5 

Statistical analysis..........................................................................................................................6 

Replication and Meta-Analysis .......................................................................................................7 

Pathway Enrichment Analysis ........................................................................................................7 

Results .................................................................................................................................. 8 

Discussion ........................................................................................................................... 10 

Conclusion .......................................................................................................................... 16 

References: ......................................................................................................................... 17 

Tables ................................................................................................................................. 21 

Figures ............................................................................................................................... 25 

Supplementary Figures ........................................................................................................ 28 

Supplementary Tables ......................................................................................................... 32 

About this Master's Thesis

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School	Rollins School of Public Health
Department	Epidemiology
Degree	M.P.H.
Submission	Master's Thesis
Language	English
Research Field	Health Sciences, Epidemiology Biology, Genetics Health Sciences, Public Health
Parola chiave	Epigenetics Interleukin 6 HIV
Committee Chair / Thesis Advisor	Yan Sun, Emory University

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