The Role of BMI-related DNA Methylations on Type II Diabetes Mellitus Among Male Veterans with HIV Open Access

Abstract

Background: People with HIV (PWH) are facing a significant burden and risk of non-communicable diseases. The increasing development of T2DM and related mortality among the HIV-infected cohort suggests a need for elucidating the association between diabetes and HIV. High body mass index (BMI) is identified as a common risk factor for T2DM among PWH in cohort studies; epigenetic studies have identified BMI-associated DNA methylation (DNAm) sites, which may lead to T2DM in general populations. However, few studies have examined the association between BMI-related methylations and T2DM among people living with HIV.

 

Method: We examined the association between BMI-related methylation sites and T2DM status among male veterans with HIV from the Veterans Aging Cohort Study (VACS). BMI-related methylation sites were identified from previous BMI EWAS in the general population and replicated among people with HIV adjusted for multiple testing. The associations were estimated with and without the adjustment by phenotypic BMI.

 

Results: Seven previously reported BMI-related DNAm were replicated among the cohort of PWH. cg11024682 (SREBF1) was significantly associated with T2DM development among the HIV-infected cohort (p-value: 4.67x10^-5, Bonferroni-corrected threshold: 7.14x10^-3). After adjusting for phenotypic BMI in the model, the association was still significant with cg11024682 (p-value: 3.59x10^-3, Bonferroni-corrected threshold: 7.14x10^-3).

 

Conclusion: Some BMI-related DNA methylation sites are associated with T2DM among PWH. The epigenetic association with T2DM may be independent from the effect of phenotypic BMI.

Table of Contents

Table of Contents

I. Background ................................................................................................................... 1

Summary of Diseases ....................................................................................................................1

T2DM Burden Among HIV-infected Cohort ................................................................................1

Risk Factors of T2DM among PWH .............................................................................................2

T2DM-Related Risk Factors .........................................................................................................3

Epigenome-Wide Association Study (EWAS) ...............................................................................4

Research Gap and Our Study .......................................................................................................6

II. Manuscript Chapter ................................................................................................... 7

Introduction .................................................................................................................................7

Method ....................................................................................................................................... 10

Results ........................................................................................................................................ 13

Discussion ................................................................................................................................... 19

III. Appendices ............................................................................................................... 22

IV. References ............................................................................................................... 29

About this Master's Thesis

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School	Rollins School of Public Health
Department	Epidemiology
Subfield / Discipline	Epidemiology - MPH & MSPH
Degree	M.P.H.
Submission	Master's Thesis
Language	English
Research Field	Health Sciences, Epidemiology
Keyword	EWAS T2DM BMI HIV
Committee Chair / Thesis Advisor	Yan V. Sun, PhD, Emory University

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