Association of Trypanolytic ApoL1 Variants with Kidney Disease in African Americans

Author:

Genovese Giulio12,Friedman David J.13,Ross Michael D.4,Lecordier Laurence5,Uzureau Pierrick5,Freedman Barry I.6,Bowden Donald W.78,Langefeld Carl D.89,Oleksyk Taras K.10,Uscinski Knob Andrea L.4,Bernhardy Andrea J.1,Hicks Pamela J.78,Nelson George W.11,Vanhollebeke Benoit5,Winkler Cheryl A.12,Kopp Jeffrey B.11,Pays Etienne5,Pollak Martin R.113

Affiliation:

1. Division of Nephrology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA.

2. Department of Mathematics, Dartmouth College, Hanover, NH 03755, USA.

3. Center for Vascular Biology Research, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA.

4. Renal Division, Department of Medicine, Brigham and Women’s Hospital (BWH), Boston, MA 02215, USA.

5. Laboratory of Molecular Parasitology, Institut de Biologie et de Médecine Moléculaires, Université Libre de Bruxelles, B-6041 Gosselies, Belgium.

6. Department of Internal Medicine/Section on Nephrology, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.

7. Department of Biochemistry and Center for Diabetes Research, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.

8. Center for Human Genomics, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.

9. Department of Biostatistical Sciences, Center for Public Health Genomics and Division of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.

10. Department of Biology, University of Puerto Rico at Mayaguez, Mayaguez, Puerto Rico 00681.

11. Kidney Disease Section, National Institute of Diabetes, Digestive, and Kidney Disease, National Institutes of Health, Bethesda, MD 20892, USA.

12. Laboratory of Genomic Diversity, SAIC-Frederick, Incorporated, National Cancer Institute–Frederick, Frederick, MD 21702, USA.

13. Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA 02142, USA.

Abstract

Out of Africa Kidney disease is more common in African Americans than in Americans of European descent, and genetics is likely to be a major contributing factor. Genovese et al. (p. 841 , published online 15 July) now show that African Americans who carry specific sequence variants in a gene on chromosome 22 encoding apolipoprotein L-1 (APOL1) have an increased risk of developing hypertension-attributed end-stage kidney disease or focal segmental glomerulosclerosis. These variants are absent from European chromosomes. Among the functions ascribed to APOL1 is the ability to lyse and kill trypanosomes. Intriguingly, APOL1 derived from the risk alleles, but not the “wild-type” allele, killed Trypanosoma brucei rhodesiense , which causes African sleeping sickness.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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