ArticleClinical epigenetics2026
APOL1 risk genotypes influence DNA methylation across multiple genomic elements in APOL1-APOL4- MYH9 region in African Americans.
Article in Clinical epigenetics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundEpigenetic modification of the APOL1 gene carrying risk alleles (G1 and G2) may represent a therapeutic strategy for APOL1-related kidney diseases. However, DNA methylation changes associated with APOL1 have not been thoroughly characterized.
methodsWe conducted an epigenome-wide association study (EWAS) of APOL1 risk alleles in 399 African Americans with chronic kidney disease (CKD) from the Atherosclerosis Risk in Communities (ARIC) study cohort using blood DNA samples. These associations were further examined in 1,677 African Americans with preserved kidney function. Additionally, the relationships between the identified CpGs and the expression of APOL1 and nearby genes were evaluated in normal kidney tissue. APOL1 risk-associated CpGs were tested for associations with estimated glomerular filtration rate based on creatinine and cystatin C (eGFR
resultsFour CpGs (cg15716373, cg16528833, cg21032535, and cg14589586) were significantly associated with APOL1 risk alleles, mapping to two enhancers and two promoters within the APOL1-APOL4-MYH9 region. Among APOL1 high-risk carriers, cg14589586 in the APOL2 promoter was inversely correlated with cg15716373 in an APOL1 intron, a pattern absent in White Americans. The association between the four CpGs and APOL1 risk alleles was also present among participants with preserved kidney function. In normal kidney tissue, cg14589586 and cg16528833 were significantly associated with the expression levels of multiple genes in this region, including APOL1 and MYH9. Multiple CpGs located within the APOL1-APOL4-MYH9 region exhibited significant joint associations with eGFR
conclusionAPOL1 risk alleles are associated with complex DNA methylation alterations across the APOL1-APOL4-MYH9 region, potentially regulating multiple genes within this locus. APOL1 risk-associated CpGs may represent therapeutic targets for APOL1-related kidney diseases.
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