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The Apolipoprotein L1 (APOL1) Gene and Nondiabetic Nephropathy in African Americans

  1. Author:
    Freedman, B. I.
    Kopp, J. B.
    Langefeld, C. D.
    Genovese, G.
    Friedman, D. J.
    Nelson, G. W.
    Winkler, C. A.
    Bowden, D. W.
    Pollak, M. R.

  2. Author Address

    [Freedman, Barry I.] Wake Forest Univ, Nephrol Sect, Sch Med, Dept Internal Med Nephrol, Winston Salem, NC 27157 USA. [Langefeld, Carl D.] Wake Forest Univ, Dept Publ Hlth Sci Biostat Sci, Sch Med, Winston Salem, NC 27157 USA. [Bowden, Donald W.] Wake Forest Univ, Dept Biochem, Sch Med, Winston Salem, NC 27157 USA. [Bowden, Donald W.] Wake Forest Univ, Ctr Diabet Res, Sch Med, Winston Salem, NC 27157 USA. [Bowden, Donald W.] Wake Forest Univ, Ctr Human Genom, Sch Med, Winston Salem, NC 27157 USA. [Kopp, Jeffrey B.] NIDDKD, Kidney Dis Sect, NIH, Bethesda, MD 20892 USA. [Genovese, Giulio; Friedman, David J.] Beth Israel Deaconess Med Ctr, Dept Internal Med Nephrol, Boston, MA 02215 USA. [Genovese, Giulio; Friedman, David J.] Harvard Univ, Sch Med, Boston, MA 02215 USA. [Winkler, Cheryl A.] NIH, Basic Res Lab, Frederick, MD USA. [Nelson, George W.] SAIC Natl Canc Inst, NIH, Frederick, MD USA. [Pollak, Martin R.] Harvard & Massachusetts Inst Technol, Broad Inst, Cambridge, MA USA.;Freedman, BI, Wake Forest Univ, Nephrol Sect, Sch Med, Dept Internal Med Nephrol, Med Ctr Blvd, Winston Salem, NC 27157 USA.;bfreedma@wfubmc.edu mpollak@bidmc.harvard.edu
    1. Year: 2010
    2. Date: Sep
  2. Journal: Journal of the American Society of Nephrology
    1. 21
    2. 9
    3. Pages: 1422-1426
  4. Type of Article: Article
  5. ISSN: 1046-6673
  1. Abstract:

    Mapping by admixture linkage disequilibrium (LD) detected strong association between nonmuscle myosin heavy chain 9 gene (MYH9) variants on chromosome 22 and nondiabetic nephropathy in African Americans. MYH9-related variants were posited to be the probable, but not necessarily the definitive, causal variants as a result of impressive statistical evidence of association, renal expression, and a role in autosomal dominant MYH9 disorders characterized by progressive glomerulosclerosis (Epstein and Fechtner syndromes). Dense mapping within MYH9 revealed striking LD patterns and racial variation in risk allele frequencies, suggesting population genetic factors such as selection may be operative in this region. Genovese and colleagues examined large chromosomal regions adjacent to MYH9 using genome-wide association methods and non-HapMap single nucleotide polymorphisms identified in Yoruba from the 1000 Genomes project. Statistically stronger associations were detected between two independent sequence variants in the Apolipoprotein L1 gene (APOL1) and nondiabetic nephropathy in African Americans, with odds ratios of 10.5 in idiopathic FSGS and 7.3 in hypertension-attributed ESRD. These kidney disease risk variants likely rose to high frequency in Africa because they confer resistance to trypanosomal infection and protect from African sleeping sickness. Risk variants in MYH9 and APOL1 are in strong LD, and the genetic risk that was previously attributed to MYH9 may reside, in part or in whole, in APOL1, although more complex models of risk cannot be excluded. This association likely explains racial disparities in nondiabetic nephropathy as a result of the high prevalence of risk alleles in individuals of African ancestry.

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External Sources

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  2. DOI: 10.1681/asn.2010070730
  3. View record in Web of Science®
  4. WOS: 000283345000008

Library Notes

  1. Fiscal Year: FY2009-2010
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