Variation inAPOL1Contributes to Ancestry-Level Differences in HDLc-Kidney Function Association
Open Access
- 1 January 2012
- journal article
- Published by Hindawi Limited in International Journal of Nephrology
- Vol. 2012, 1-10
- https://doi.org/10.1155/2012/748984
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,), West Africans (WA,), and African Americans (AA,). There were significant differences by ancestry: HDLc was positively associated with eGFR in HC (,), but negatively associated among African ancestry populations (WA: −0.19,; AA: −0.09,). These differences were also seen in nationally-representative NHANES data (among European Americans: 0.09,; among African Americans −0.14,). 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;). 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 theAPOL1× HDLc interaction among AA, genetic factors may contribute to this paradoxical association. Notably, these findings suggest that the unexplained mechanism by whichAPOL1affects kidney-disease risk may involve HDLc.
Keywords
Funding Information
- NIGMS/MBRS/SCORE Program (S06GM008016-320107, S06GM008016-380111, 2M01RR010284, CRGGH—Z01HG200362)
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