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Clin Infect Dis. 2019 Mar 20. pii: ciz240. doi: 10.1093/cid/ciz240. [Epub ahead of print]

Epigenetic Associations with Estimated Glomerular Filtration Rate (eGFR) among Men with HIV Infection.

Author information

1
Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, USA.
2
Boston University School of Medicine, Boston, MA, USA.
3
Cardiovascular Medicine Division, Vanderbilt University School of Medicine and Tennessee Valley Healthcare System, Nashville, TN, USA.
4
Connecticut Veteran Health System, West Haven, CT, USA.
5
Yale University School of Medicine, New Haven, CT, USA.
6
Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA.
7
Hubert Department of Global Health, Rollins School of Public Health, Emory University, Atlanta, Georgia, USA.
8
Division of Infectious Diseases, Emory University School of Medicine, Atlanta, GA, USA.
9
Atlanta Veterans Affairs Healthcare System, Decatur, GA, USA.
10
Department of Biomedical Informatics, Emory University School of Medicine, Atlanta, GA, USA.

Abstract

BACKGROUND:

People living with human immunodeficiency virus (HIV) infection have higher risk for chronic kidney disease (CKD), defined by a reduced estimated glomerular filtration rate (eGFR). Previous studies have implicated epigenetic changes related to CKD; however, the mechanism of HIV-related CKD has not been thoroughly investigated.

METHODS:

We conducted an epigenome-wide association study of eGFR among 567 HIV-positive and 117 HIV-negative male participants in the Veterans Aging Cohort Study (VACS) to identify epigenetic signatures of kidney function.

RESULTS:

By surveying over 400,000 CpG sites measured from peripheral blood mononuclear cells, we identified 15 sites significantly associated with eGFR (false discovery rate q-value < 0.05) among HIV-positive participants. The most significant CpG sites, located at MAD1L1, TSNARE1/BAI1, and LTV1, were all negatively associated with eGFR (cg06329547: p-value 5.2510-9; cg23281907: p-value 1.3710-8; cg18368637: p-value 5.1710-8). We also replicated previously reported eGFR-associated CpG sites including cg17944885 (p-value of 2.510-5) located between ZNF788 and ZNF20 on chromosome 19 in the pooled population.

CONCLUSION:

Our study uncovered novel epigenetic associations with kidney function among people living with HIV and suggested potential epigenetic mechanisms linked with HIV-related CKD risk.

KEYWORDS:

EWAS; HIV infection; VACS; eGFR; renal function

PMID:
30893429
DOI:
10.1093/cid/ciz240

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