Epigenetic Association with Estimated Glomerular Filtration Rate (eGFR) among HIV-infected Individuals 公开

Abstract

People living with human immunodeficiency virus (HIV) infection have higher risk for chronic kidney disease (CKD), defined by reduced estimated glomerular filtration rate (eGFR). Previous studies have implicated epigenetic changes contributing to CKD, however, mechanism of HIV-related CKD has not been thoroughly investigated. We conducted an epigenome-wide association studies of eGFR among 567 HIV-infected and 117 HIV-uninfected Veterans Aging Cohort Study (VACS) participants to identify epigenetic signatures of kidney function. By surveying over 400,000 CpG sites measured on peripheral blood, we identified 15 and 16 sites significantly associated with eGFR (false discovery rate q-value < 0.05) among the HIV-infected and total study population, respectively. The most significant CpG sites, located at MAD1L1, TSNARE1/BAI1, and LTV1, were all negatively associated with eGFR (cg06329547: p-value of 5.25´10^-9; cg23281907: p-value of 1.37´10^-8; cg18368637: p-value of 5.17´10^-8). These identified associations were not significant among HIV-uninfected participants. We also replicated previously reported eGFR-associated CpG sites including cg17944885 located between ZNF788 and ZNF20 on chromosome 19 (p-value of 2.5´10^-5). Our findings highlighted novel epigenetic associations with kidney function among people living with HIV, and suggested potential epigenetic mechanism linked with HIV-related CKD risk.

 

Table of Contents

Literature Review 1-2

Introduction 3-5

Methods 6-10

Results 10-13

Discussion 13-20

Tables 21-24

Figures 25-26

Reference 27-37

About this Dissertation

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School	Rollins School of Public Health
Department	Epidemiology
Subfield / Discipline	Epidemiology - MPH & MSPH
Degree	M.P.H.
Submission	Dissertation
Language	English
Research Field	Biology, Bioinformatics Health Sciences, Public Health Health Sciences, Epidemiology
关键词	HIV, CKD, Epigenetic, DNA methylation
Committee Chair / Thesis Advisor	Yan Sun, Emory University
Partnering Agencies	Does not apply (no collaborating organization)

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