title: Variation in APOL1 Contributes to Ancestry-Level Differences in HDLc-Kidney Function Association.
abstract: Low levels of high-density cholesterol (HDLc) accompany chronic kidney disease, but the association between HDLc and the estimated glomerular filtration rate (eGFR) in the general population is unclear. We investigated the HDLc-eGFR association in nondiabetic Han Chinese (HC, n = 1100), West Africans (WA, n = 1497), and African Americans (AA, n = 1539). There were significant differences by ancestry: HDLc was positively associated with eGFR in HC (β = 0.13, P < 0.0001), but negatively associated among African ancestry populations (WA: -0.19, P < 0.0001; AA: -0.09, P = 0.02). These differences were also seen in nationally-representative NHANES data (among European Americans: 0.09, P = 0.005; among African Americans -0.14, P = 0.03). To further explore the findings in African ancestry populations, we investigated the role of an African ancestry-specific nephropathy risk variant, rs73885319, in the gene encoding HDL-associated APOL1. Among AA, an inverse HDLc-eGFR association was observed only with the risk genotype (-0.38 versus 0.001; P = 0.03). This interaction was not seen in WA. In summary, counter to expectation, an inverse HDLc-eGFR association was observed among those of African ancestry. Given the APOL1 × HDLc interaction among AA, genetic factors may contribute to this paradoxical association. Notably, these findings suggest that the unexplained mechanism by which APOL1 affects kidney-disease risk may involve HDLc.
authors.affiliation: Center for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892-5635, USA.
authors.forename: Amy Rebecca
authors.initials: AR
authors.lastname: Bentley
authors.forename: Ayo P
authors.initials: AP
authors.lastname: Doumatey
authors.forename: Guanjie
authors.initials: G
authors.lastname: Chen
authors.forename: Hanxia
authors.initials: H
authors.lastname: Huang
authors.forename: Jie
authors.initials: J
authors.lastname: Zhou
authors.forename: Daniel
authors.initials: D
authors.lastname: Shriner
authors.forename: Congqing
authors.initials: C
authors.lastname: Jiang
authors.forename: Zhenjian
authors.initials: Z
authors.lastname: Zhang
authors.forename: Guozheng
authors.initials: G
authors.lastname: Liu
authors.forename: Olufemi
authors.initials: O
authors.lastname: Fasanmade
authors.forename: Thomas
authors.initials: T
authors.lastname: Johnson
authors.forename: Johnnie
authors.initials: J
authors.lastname: Oli
authors.forename: Godfrey
authors.initials: G
authors.lastname: Okafor
authors.forename: Benjamin A
authors.initials: BA
authors.lastname: Eghan
authors.forename: Kofi
authors.initials: K
authors.lastname: Agyenim-Boateng
authors.forename: Jokotade
authors.initials: J
authors.lastname: Adeleye
authors.forename: Williams
authors.initials: W
authors.lastname: Balogun
authors.forename: Clement
authors.initials: C
authors.lastname: Adebamowo
authors.forename: Albert
authors.initials: A
authors.lastname: Amoah
authors.forename: Joseph
authors.initials: J
authors.lastname: Acheampong
authors.forename: Adebowale
authors.initials: A
authors.lastname: Adeyemo
authors.forename: Charles N
authors.initials: CN
authors.lastname: Rotimi