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MYH9 is a major-effect risk gene for focal segmental glomerulosclerosis

  1. Author:
    Kopp, J. B.
    Smith, M. W.
    Nelson, G. W.
    Johnson, R. C.
    Freedman, B. I.
    Bowden, D. W.
    Oleksyk, T.
    McKenzie, L. M.
    Kajiyama, H.
    Ahuja, T. S.
    Berns, J. S.
    Briggs, W.
    Cho, M. E.
    Dart, R. A.
    Kimmel, P. L.
    Korbet, S. M.
    Michel, D. M.

  2. Author Address

    Smith, Michael W.; Nelson, George W.; Johnson, Randall C.; Oleksyk, Taras, McKenzie, Louise M.; Winkler, Cheryl A.] NCI, Lab Genom Divers, SAIC Frederick, Frederick, MD 21702 USA. [Kopp, Jeffrey B.; Kajiyama, Hiroshi, Cho, Monique E.] NIDDK, Kidney Dis Sect, NIH, Bethesda, MD 20892 USA. [Freedman, Barry I.; Bowden, Donald W.] Wake Forest Univ, Bowman Gray Sch Med, Nephrol Sect, Winston Salem, NC 27157 USA. [Ahuja, Tejinder S.] Univ Texas Galveston, Med Branch, Galveston, TX 77555 USA. [Berns, Jeffrey S.] Univ Penn, Sch Med, Renal Electrolyte & Hypertens Div, Philadelphia, PA 19104 USA. [Briggs, William] William Beaumont Hosp, Royal Oak, MI 48073 USA. [Dart, Richard A.] Marshfield Clin Fdn Med Res & Educ, Dept Hypertens & Nephrol, Marshfield, WI 54449 USA. [Kimmel, Paul L.] George Washington Univ, Med Ctr, Div Renal Dis & Hypertens, Dept Med, Washington, DC 20037 USA. [Korbet, Stephen M.] Rush Univ, Med Ctr, Dept Med, Chicago, IL 60612 USA. [Michel, Donna M.] Hypertens & Kidney Specialists, Lancaster, PA 17601 USA. [Mokrzycki, Michele H.] Albert Einstein Coll Med, Div Nephrol, Bronx, NY 10461 USA. [Schelling, Jeffrey R.] Case Western Reserve Univ, Dept Med, Cleveland, OH 44109 USA. [Simon, Eric] Tulane Univ, Sch Med, Nephrol Sect, New Orleans, LA 70112 USA. [Trachtman, Howard] Schneider Childrens Hosp Syst, Div Nephrol, Dept Pediat, New Hyde Pk, NY 11040 USA. [Vlahov, David] New York Acad Med, New York, NY 10029 USA.
    1. Year: 2008
  2. Journal: Nature Genetics
    1. 40
    2. 10
    3. Pages: 1175-1184
  4. Type of Article: Article
  1. Abstract:

    The increased burden of chronic kidney and end-stage kidney diseases (ESKD) in populations of African ancestry has been largely unexplained. To identify genetic variants predisposing to idiopathic and HIV-1-associated focal segmental glomerulosclerosis (FSGS), we carried out an admixture-mapping linkage-disequilibrium genome scan on 190 African American individuals with FSGS and 222 controls. We identified a chromosome 22 region with a genome-wide logarithm of the odds (lod) score of 9.2 and a peak lod of 12.4 centered on MYH9, a functional candidate gene expressed in kidney podocytes. Multiple MYH9 SNPs and haplotypes were recessively associated with FSGS, most strongly a haplotype spanning exons 14 through 23 (OR = 5.0, 95% CI 3.5-7.1, P = 4 x 10(-23), n = 852). This association extended to hypertensive ESKD (OR = 2.2, 95% CI = 1.5-3.4, n = 433), but not type 2 diabetic ESKD (n 476). Genetic variation at the MYH9 locus substantially explains the increased burden of FSGS and hypertensive ESKD among African Americans.

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External Sources

  1. PMID: 18794856

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