New Gene Variant Identified for End Stage Renal Disease
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
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.
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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