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Association of Trypanolytic ApoL1 Variants with Kidney Disease in African Americans

  1. Author:
    Genovese, G.
    Friedman, D. J.
    Ross, M. D.
    Lecordier, L.
    Uzureau, P.
    Freedman, B. I.
    Bowden, D. W.
    Langefeld, C. D.
    Oleksyk, T. K.
    Knob, A. L. U.
    Bernhardy, A. J.
    Hicks, P. J.
    Nelson, G. W.
    Vanhollebeke, B.
    Winkler, C. A.
    Kopp, J. B.
    Pays, E.
    Pollak, M. R.

  2. Author Address

    [Genovese, Giulio; Friedman, David J.; Bernhardy, Andrea J.; Pollak, Martin R.] Beth Israel Deaconess Med Ctr, Dept Med, Div Nephrol, Boston, MA 02215 USA. [Genovese, Giulio; Friedman, David J.; Bernhardy, Andrea J.; Pollak, Martin R.] Harvard Univ, Sch Med, Boston, MA 02215 USA. [Genovese, Giulio] Dartmouth Coll, Dept Math, Hanover, NH 03755 USA. [Friedman, David J.] Beth Israel Deaconess Med Ctr, Dept Med, Vasc Biol Res Ctr, Boston, MA 02215 USA. [Ross, Michael D.; Knob, Andrea L. Uscinski] Brigham & Womens Hosp, Dept Med, Div Renal, Boston, MA 02215 USA. [Lecordier, Laurence; Uzureau, Pierrick; Vanhollebeke, Benoit; Pays, Etienne] Univ Libre Bruxelles, Inst Biol & Med Mol, Mol Parasitol Lab, B-6041 Gosselies, Belgium. [Freedman, Barry I.] Wake Forest Univ, Sch Med, Nephrol Sect, Dept Internal Med, Winston Salem, NC 27157 USA. [Bowden, Donald W.; Hicks, Pamela J.] Wake Forest Univ, Sch Med, Dept Biochem, Winston Salem, NC 27157 USA. [Bowden, Donald W.; Hicks, Pamela J.] Wake Forest Univ, Sch Med, Ctr Diabet Res, Winston Salem, NC 27157 USA. [Bowden, Donald W.; Langefeld, Carl D.; Hicks, Pamela J.] Wake Forest Univ, Sch Med, Ctr Human Genom, Winston Salem, NC 27157 USA. [Langefeld, Carl D.] Wake Forest Univ, Sch Med, Ctr Publ Hlth Genom, Dept Biostat Sci, Winston Salem, NC 27157 USA. [Langefeld, Carl D.] Wake Forest Univ, Sch Med, Div Publ Hlth Sci, Winston Salem, NC 27157 USA. [Oleksyk, Taras K.] Univ Puerto Rico, Dept Biol, Mayaguez, PR 00681 USA. [Nelson, George W.; Kopp, Jeffrey B.] NIDDKD, Kidney Dis Sect, NIH, Bethesda, MD 20892 USA. [Winkler, Cheryl A.] NCI, Lab Genom Divers, SAIC Frederick Inc, Frederick, MD 21702 USA. [Pollak, Martin R.] Broad Inst Harvard & MIT, Cambridge, MA 02142 USA.;Pollak, MR, Beth Israel Deaconess Med Ctr, Dept Med, Div Nephrol, Boston, MA 02215 USA.;epays@ulb.ac.be mpollak@bidmc.harvard.edu
    1. Year: 2010
    2. Date: Aug
  2. Journal: Science
    1. 329
    2. 5993
    3. Pages: 841-845
  4. Type of Article: Article
  5. ISSN: 0036-8075
  1. Abstract:

    African Americans have higher rates of kidney disease than European Americans. Here, we show that, in African Americans, focal segmental glomerulosclerosis (FSGS) and hypertension-attributed end-stage kidney disease (H-ESKD) are associated with two independent sequence variants in the APOL1 gene on chromosome 22 {FSGS odds ratio = 10.5 [95% confidence interval (CI) 6.0 to 18.4]; H-ESKD odds ratio = 7.3 (95% CI 5.6 to 9.5)}. The two APOL1 variants are common in African chromosomes but absent from European chromosomes, and both reside within haplotypes that harbor signatures of positive selection. ApoL1 (apolipoprotein L-1) is a serum factor that lyses trypanosomes. In vitro assays revealed that only the kidney disease-associated ApoL1 variants lysed Trypanosoma brucei rhodesiense. We speculate that evolution of a critical survival factor in Africa may have contributed to the high rates of renal disease in African Americans.

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External Sources

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  2. DOI: 10.1126/science.1193032
  3. View record in Web of Science®
  4. WOS: 000280809900051

Library Notes

  1. Fiscal Year: FY2009-2010
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