By Tim Parsons
School of Public Health

Scientists at the Johns Hopkins schools of Public Health and Medicine have, for the first time, identified variants in the gene MYH9 that are associated with increased risk for nondiabetic end stage renal disease, which is the near-loss of kidney function leading to either dialysis or transplant.

MYH9, located on chromosome 22, is the first gene identified for common forms of kidney disease. The study was published online Sept. 14 in the journal Nature Genetics and in the October print edition. In a separate study published in the same issue, researchers at the National Institutes of Health report similar findings.

In the United States, about 26 million Americans have chronic kidney disease, with nearly 427,000 Americans requiring dialysis or kidney transplant each year for the treatment of end stage renal disease, according to government studies. African-Americans are affected disproportionately as they have a four times higher incidence of end stage renal disease compared to European-Americans.

"We are in the midst of an epidemic of chronic kidney disease, in which African-Americans are disproportionately affected. This finding does not mean that nongenetic factors, such as socioeconomic indicators and other factors, do not contribute to the higher risk of kidney disease in African-Americans. It defines a subset of persons most likely vulnerable to the harmful effect of these factors," said study author Michael J. Klag, dean of the Johns Hopkins Bloomberg School of Public Health.

Lead author Linda Kao, associate professor in the Bloomberg School's Department of Epidemiology and the Welch Center for Prevention, Epidemiology and Clinical Research, said, "Our results show that in addition to environmental and behavioral risk factors, genetic factors play a role as well. While we know these genetic variations are common among African-Americans, not everyone with the variations has disease, and not everyone with disease has the variations," she said. "Therefore, it is imperative that we understand what other modifiable risk factors are interacting with the genetic risk factors to cause disease."

For the study, researchers used a technique known as admixture mapping to survey genomes of 1,372 African-Americans with end stage renal disease and a control group of about 800 African- Americans without ESRD. The study identified several alleles, or variations, in the MYH9 gene that were highly associated with nondiabetic ESRD but not diabetic ESRD. Even though the variations identified in this study are present in many populations, they are more frequent among individuals of West African ancestry.

"This finding suggests that the mechanisms leading from onset of chronic kidney disease to kidney failure may differ based on the inciting cause," said study author Rulan S. Parekh, associate professor at the School of Medicine and the Welch Center. "Discovery of the gene and its association with kidney disease will lead to future studies to better understand the biology of kidney disease progression and ultimately may direct drug therapy and potential screening of patients."

Additional authors are Lucy A. Meoni, David Reich, Yvette Berthier-Schaad, Man Li, Josef Coresh, Nick Patterson, Arti Tandon; Neil R. Powe, Nancy E. Fink; John H. Sadler, Matthew R. Weir, Hanna E. Abboud, Sharon Adler, Jasmin Divers, Sudha K. Iyengar, Barry I. Freedman, Paul L. Kimmel, William C. Knowler, Orly F. Kohn, Kristopher Kramp, David J. Leehey, Susanne Nicholas, Madeleine Pahl, Jeffrey R. Schelling, John R. Sedor, Denyse Thornly-Brown, Cheryl A. Winkler and Michael W. Smith.

The research was supported by grants from the National Institutes of Health and the National Cancer Institute's Center for Cancer Research.

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