Variation in APOL1 Contributes to Ancestry-Level Differences in HDLc-Kidney Function Association
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.
Cholesterol , Kidney disease , Genetic factors , Research Subject Categories::MEDICINE
Bentley AR, Doumatey AP, Chen G, Huang H, Zhou J, Shriner D, Jiang C, Zhang Z, Liu G, Fasanmade O, Johnson T, Oli J, Okafor G, Eghan BA Jr, Agyenim-Boateng K, Adeleye J, Balogun W, Adebamowo C, Amoah A, Acheampong J, Adeyemo A, Rotimi CN. Variation in APOL1 Contributes to Ancestry-Level Differences in HDLc-Kidney Function Association. Int J Nephrol. 2012;2012:748984. doi: 10.1155/2012/748984