Seminars in Nephrology
Volume 30, Issue 4 , Pages 409-417 , July 2010

MYH9 Genetic Variants Associated With Glomerular Disease: What Is the Role for Genetic Testing?

  • Jeffrey B. Kopp, MD

      Affiliations

    • Kidney Disease Section, Kidney Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD
    • Corresponding Author InformationAddress reprint requests to Jeffrey Kopp, MD, 10 Center Dr, MSC 1268, National Institutes of Health, Bethesda, MD 20892-1268
    • ,
  • Cheryl A. Winkler, PhD

      Affiliations

    • Science Applications International Corporation and Center for Cancer Research, National Cancer Institutes, National Institutes of Health, Frederick, MD
    • ,
  • George W. Nelson, PhD

      Affiliations

    • Science Applications International Corporation and Center for Cancer Research, National Cancer Institutes, National Institutes of Health, Frederick, MD

References 

  1. Kopp JB, Smith MW, Nelson GW, et al. MYH9 is a major-effect risk gene for focal segmental glomerulosclerosis. Nat Genet. 2008;40:1175–1184
  2. Kao WH, Klag MJ, Meoni LA, et al. MYH9 is associated with nondiabetic end-stage renal disease in African Americans. Nat Genet. 2008;40:1185–1192
  3. Freedman BI, Hicks PJ, Bostrom MA, et al. Polymorphisms in the non-muscle myosin heavy chain 9 gene (MYH9) are strongly associated with end-stage renal disease historically attributed to hypertension in African Americans. Kidney Int. 2009;75:736–745
  4. Freedman BI, Kopp JB, Winkler CA, et al. Polymorphisms in the nonmuscle myosin heavy chain 9 gene (MYH9) are associated with albuminuria in hypertensive African Americans: the HyperGEN study. Am J Nephrol. 2009;29:626–632
  5. Freedman BI, Hicks PJ, Bostrom MA, et al. Non-muscle myosin heavy chain 9 gene MYH9 associations in African Americans with clinically diagnosed type 2 diabetes mellitus-associated ESRD. Nephrol Dial Transplant. 2009;24:3366–3371
  6. Pollard TD, Cooper JA. Actin, a central player in cell shape and movement. Science. 2009;326:1208–1212
  7. Foth BJ, Goedecke MC, Soldati D. New insights into myosin evolution and classification. Proc Natl Acad Sci U S A. 2006;103:3681–3686
  8. Perry J, Tam S, Zheng K, et al. Type IV collagen induces podocytic features in bone marrow stromal stem cells in vitro. J Am Soc Nephrol. 2006;17:66–76
  9. Saleem MA, Zavadil J, Bailly M, et al. The molecular and functional phenotype of glomerular podocytes reveals key features of contractile smooth muscle cells. Am J Physiol Renal Physiol. 2008;295:F959–F970
  10. Seri M, Pecci A, Di Bari F, et al. MYH9-related disease: May-Hegglin anomaly, Sebastian syndrome, Fechtner syndrome, and Epstein syndrome are not distinct entities but represent a variable expression of a single illness. Medicine (Baltimore). 2003;82:203–215
  11. Ghiggeri GM, Caridi G, Magrini U, et al. Genetics, clinical and pathological features of glomerulonephritis associated with mutations of nonmuscle myosin IIA (Fechtner syndrome). Am J Kidney Dis. 2003;41:95–104
  12. Vicente-Manzanares M, Ma X, Adelstein RS, et al. Non-muscle myosin II takes centre stage in cell adhesion and migration. Nat Rev Mol Cell Biol. 2009;10:778–790
  13. Nelson GW, Freedman BI, Bowden DW, et al. Dense mapping of MYH9 localizes the strongest kidney disease associations to the region of introns 13 to 15. Hum Mol Genet. 19:1805-15.
  14. Shahinian V, Rajaraman S, Borucki M, et al. Prevalence of HIV-associated nephropathy in autopsies of HIV-infected patients. Am J Kidney Dis. 2000;35:884–888
  15. Strauss J, Abitbol C, Zilleruelo G, et al. Renal disease in children with the acquired immunodeficiency syndrome. N Engl J Med. 1989;321:625–630
  16. Kitiyakara C, Kopp JB, Eggers P. Trends in the epidemiology of focal segmental glomerulosclerosis. Sem Nephrol. 2003;23:172–182
  17. United States Census Bureau. 2010 Statistical Abstract: USA Statistics in Brief. www.census.gov/compendia/statab/brief.htmlAccessed 12 July 2010
  18. Troyanov S, Wall CA, Miller JA, et al. Focal and segmental glomerulosclerosis: definition and relevance of a partial remission. J Am Soc Nephrol. 2005;16:1061–1068
  19. US Renal Data System. USRDS 2009 annual data report: atlas of end-stage renal disease in the United States. Bethesda, MD: National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases; 2009;
  20. Gupta SK, Eustace JA, Winston JA, et al. Guidelines for the management of chronic kidney disease in HIV-infected patients: recommendations of the HIV Medicine Association of the Infectious Diseases Society of America. Clin Infect Dis. 2005;40:1559–1585
  21. Feuer EJ, Wun LM, Boring CC, et al. The lifetime risk of developing breast cancer. J Natl Cancer Inst. 1993;85:892–897
  22. Merrill RM, Feuer EJ. Risk-adjusted cancer-incidence rates (United States). Cancer Causes Control. 1996;7:544–552
  23. Lipkowitz MS, Iyengar SK, Molineros J, et al. Association analysis of MYH9 in hypertensive nephropathy: Results from the AASK study. J Am Soc Nephrol. 2009;20:56A
  24. Genovese G, Friedman DJ, Ross MD, et al. Association of trypanolytic ApoL1 variants with kidney disease in African Americans. Science Express. 15 July 2010;
  25. Winkler CA, Nelson G, Oleksyk TK, Nava MB, Kopp JB. Genetics of focal segmental glomerulosclerosis and human immunodeficiency virus-associated collapsing glomerulopathy: The role of MYH9 genetic variation. Semin Nephrol. 2010;30:111–125
  26. Kopp JB. Glomerular pathology in autosomal dominant MYH9 spectrum disorders: what are the clues telling us about disease mechanism?. Kidney Int. 2010;78:130–133

 The National Institutes of Health, together with all three authors, has applied for a patent on MYH9 SNPs associated with the diseases described here.

 This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under contract N01-CO-12400, and the Intramural Research Program of the National Institute for Diabetes, Digestive, and Kidney Diseases (ZO-1 DK043308). The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, and mention of trade names, commercial products, or organizations does not imply endorsement by the US Government. The publisher or recipient acknowledges right of the US Government to retain a nonexclusive, royalty-free license in and to any copyright covering the article.

PII: S0270-9295(10)00099-9

doi: 10.1016/j.semnephrol.2010.06.007

Seminars in Nephrology
Volume 30, Issue 4 , Pages 409-417 , July 2010

Article Tools

* Image Usage & Resolution