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

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.