Skip NavigationSkip to Content

Variants in the Wilms' tumor gene are associated with focal segmental glomerulosclerosis in the African American population

  1. Author:
    Orloff, M. S.
    Iyengar, S. K.
    Winkler, C. A.
    Goddard, K. A. B.
    Dart, R. A.
    Ahuja, T. S.
    Mokrzycki, M.
    Briggs, W. A.
    Korbet, S. M.
    Kimmel, P. L.
    Simon, E. E.
    Trachtman, H.
    Vlahov, D.
    Michel, D. M.
    Berns, J. S.
    Smith, M. C.
    Schelling, J. R.
    Sedor, J. R.
    Kopp, J. B.
  2. Author Address

    Case Western Reserve Univ, Dept Epidemiol & Biostat, Cleveland, OH 44106 USA. NCI, Lab Genom Divers, Frederick, MD 21701 USA. NCI, Basic Res Program, Sci Applicat Int Corp, NIH, Frederick, MD 21701 USA. Marshfield Clin Fdn Med Res & Educ, Dept Hypertens & Nephrol, Marshfield, WI 54449 USA. Univ Texas, Med Branch, Dept Med, Div Nephrol, Galveston, TX 77550 USA. Albert Einstein Coll Med, Div Nephrol, Bronx, NY 10467 USA. Johns Hopkins Univ, Sch Med, Div Nephrol, Baltimore, MD USA. Rush Univ, Med Ctr, Dept Med, Chicago, IL 60612 USA. George Washington Univ, Med Ctr, Dept Med, Div Renal Dis & Hypertens, Washington, DC 20037 USA. Tulane Univ, Sch Med, Nephrol Sect, New Orleans, LA 70112 USA. Schneider Childrens Hosp, Dept Pediat, Div Nephrol, New Hyde Pk, NY USA. New York Acad Med, Ctr Urban Epidemiol Studies, New York, NY USA. W Virginia Univ, Dept Med, Morgantown, WV 26506 USA. Univ Penn, Renal Electrolyte & Hypertens Div, Philadelphia, PA 19104 USA. Univ Hosp Cleveland, Div Nephrol & Hypertens, Cleveland, OH 44106 USA. Case Western Reserve Univ, Dept Med, Cleveland, OH 44106 USA. MetroHlth Syst, Rammelkamp Ctr Res & Educ, Kidney Dis Res Ctr, Cleveland, OH USA. NIDDKD, Kidney Dis Sect, Kidney Dis Branch, NIH,US Dept HHS, Bethesda, MD 20892 USA Iyengar, SK, Case Western Reserve Univ, Dept Epidemiol & Biostat, Wolstein Res Bldg 1315,10900 Euclid Ave, Cleveland, OH 44106 USA
    1. Year: 2005
    2. Date: APR 14
  1. Journal: Physiological Genomics
    1. 21
    2. 2
    3. Pages: 212-221
  2. Type of Article: Article
  1. Abstract:

    Wilms' tumor gene (WT1) is important for nephrogenesis and gonadal growth. WT1 mutations cause Denys-Drash and Frasier syndromes, which are characterized by glomerular scarring. To test whether genetic variations in WT1 and WIT1 (gene immediately 5' to WT1) associate with focal segmental glomerulosclerosis (FSGS), patients with biopsy-proven idiopathic and HIV-1-associated FSGS were enrolled in a multicenter study. We genotyped SNP rs6508 located in WIT1 exon 1, three SNPs (rs2301250, rs2301252, rs2301254) in the promoter shared by WT1 and WIT1, rs2234590 in exon 6, rs2234591 in intron 6, rs16754 in exon 7, and rs1799937 in intron 9 of WT1. Cases (n = 218) and controls (n = 281) were compared in the African American population. Stratification by HIV-1 infection status showed that SNPs rs6508, rs2301254, and rs1799937 were significantly associated with FSGS [rs6508 odds ratio (OR) 1.82, P = 0.006; rs2301254 OR 1.65, P = 0.049; rs1799937 OR 1.91, P = 0.005] in the non-HIV-1 group and rs2234591 (OR 0.234, P = 0.011) in the HIV-1 group. Haplotype analyses in the population revealed that seven SNPs were associated with FSGS; five SNPs had the highest contingency score [-log(10)(P value) = 13.57] in the HIV-1 group. This association could not be explained by population substructure. We conclude that SNPs in WT1 and WIT1 genes are significantly associated with FSGS, suggesting that variants in these genes may mediate pathogenesis by altering WT1 function. Furthermore, HIV-1 infection status interacts with genetic variations in both genes to influence this phenotype. We speculate that nephropathy liability alleles in WT1 pathway genes cause podocyte dysfunction and glomerular scarring

    See More

External Sources

  1. WOS: 000228387600009

Library Notes

  1. No notes added.
NCI at Frederick

You are leaving a government website.

This external link provides additional information that is consistent with the intended purpose of this site. The government cannot attest to the accuracy of a non-federal site.

Linking to a non-federal site does not constitute an endorsement by this institution or any of its employees of the sponsors or the information and products presented on the site. You will be subject to the destination site's privacy policy when you follow the link.

ContinueCancel