Epigenetic Associations With Estimated Glomerular Filtration Rate Among Men With Human Immunodeficiency Virus 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 to identify epigenetic signatures of kidney function. Results. By surveying more than 400 000 cytosine guanine dinucleotide (CpG) sites measured from peripheral blood mononuclear cells, we identified 15 sites that were 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 = 5.25 x 10(-9); cg23281907, P = 1.37 x 10(-8); cg18368637, P = 5.17 x 10(-8)). We also replicated previously reported eGFR-associated CpG sites including cg17944885 (P = 2.5 x 10(-5)) located between ZNF788 and ZNF20 on chromosome 19 in the pooled population. Conclusions. In this study we uncovered novel epigenetic associations with kidney function among people living with HIV and suggest potential epigenetic mechanisms linked with HIV-related CKD risk.