Table of Contents Author Guidelines Submit a Manuscript
International Journal of Nephrology
Volume 2012, Article ID 748984, 10 pages
http://dx.doi.org/10.1155/2012/748984
Clinical Study

Variation in APOL1 Contributes to Ancestry-Level Differences in HDLc-Kidney Function Association

1Center for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892-5635, USA
2Suizhou Central Hospital, Suizhou, Hubei 441300, China
3Department of Medicine, University of Lagos, Lagos 101017, Nigeria
4Department of Medicine, University of Nigeria Teaching Hospital, Enugu 400001, Nigeria
5Department of Medicine, University of Science and Technology, Kumasi, Ghana
6Department of Medicine, University of Ibadan, Ibadan 200284, Nigeria
7Department of Medicine and Therapeutics, University of Ghana Medical School, Accra, Ghana

Received 7 February 2012; Revised 26 June 2012; Accepted 11 July 2012

Academic Editor: Rudolph A. Rodriguez

Copyright © 2012 Amy Rebecca Bentley et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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 = 1 1 0 0 ), West Africans (WA, 𝑛 = 1 4 9 7 ), and African Americans (AA, 𝑛 = 1 5 3 9 ). There were significant differences by ancestry: HDLc was positively associated with eGFR in HC ( 𝛽 = 0 . 1 3 , 𝑃 < 0 . 0 0 0 1 ), but negatively associated among African ancestry populations (WA: −0.19, 𝑃 < 0 . 0 0 0 1 ; AA: −0.09, 𝑃 = 0 . 0 2 ). These differences were also seen in nationally-representative NHANES data (among European Americans: 0.09, 𝑃 = 0 . 0 0 5 ; among African Americans −0.14, 𝑃 = 0 . 0 3 ). 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 . 0 3 ). 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.