Genetics of kidney failure and the evolving story of APOL1
David J. Friedman, Martin R. Pollak
David J. Friedman, Martin R. Pollak
Published September 1, 2011
Citation Information: J Clin Invest. 2011;121(9):3367-3374. https://doi.org/10.1172/JCI46263.
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Science in Medicine

Genetics of kidney failure and the evolving story of APOL1

Abstract

Chronic kidney disease (CKD) results from a wide array of processes that impair the kidney’s ability to perform its major functions. As many as 20 million Americans suffer from CKD and nearly a half million from end-stage renal disease, but there are also examples of centenarians with adequate renal function. Family-based and genome-wide studies suggest that genetic differences substantially influence an individual’s lifetime risk for kidney disease. One emerging theme is that evolution of genes related to host defense against pathogens may limit kidney longevity. The identification of these genetic factors will be critical for expanding our understanding of renal development and function as well as for the design of novel therapeutics for kidney disease.

Authors

David J. Friedman, Martin R. Pollak

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Figure 1

APOL1 risk variants: admixture and MALD.

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APOL1 risk variants: admixture and MALD. (A) APOL1 risk variants ar...
(A) APOL1 risk variants arose approximately 4,000 years ago in Africa and rose quickly to high frequency. In Yoruba (Nigeria), approximately 46% of chromosomes contain either the G1 or G2 allele. The ancestors of modern Europeans left Africa many millennia before the origin of these risk alleles, so the risk alleles are not found in Europeans. Today, approximately 36% of all African Americans (AA) carry the G1 or G2 alleles. (B) MALD. In the US, African Americans have roughly 80% African ancestry and 20% European ancestry. Since African Americans have much more renal disease than European Americans, MALD tests for chromosomal regions in African Americans with renal disease (cases) that are disproportionately African in origin. Genome-wide, there is no excess African ancestry in renal disease cases. However, at the chromosome 22 locus, there is a marked excess of African ancestry in cases. The odds of this distribution by chance alone are several billion to one (41, 42).