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New Gene Variant identified for non-Diabetic
End Stage Renal Disease in African Americans
Newswise — MYH9, located on the 22
chromosome, is the first gene identified for
common forms of kidney disease.
The study was published
online September 14 in the journal Nature
Genetics and will be published in the
October print edition.
In a separate study published
in the same issue, researchers at the
National Institutes of Health reported
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 ESRD, according to
U.S. 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 non-genetic
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, MD, MPH, dean of the
Johns Hopkins Bloomberg School of Public
Health.
“Our results show that in
addition to environmental and behavioral
risk factors, genetic factors play a role as
well,” said lead author, Linda Kao, PhD, MHS,
associate professor in Bloomberg School of
Public Health’s Department of Epidemiology
and the Welch Center for Prevention,
Epidemiology and Clinical Research.
“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.
"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 ESRD 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
non-diabetic ESRD but not diabetic ESRD.
These variants were not
associated with diabetic ESRD. Even though
the variations identified in this study are
present in many populations, they are more
frequent among individuals with 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, MD, associate
professor Johns Hopkins 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 include
Lucy A. Meoni, ScM; David Reich, PhD; Yvette
Berthier-Schaad, PhD; Man Li, MS; Josef
Coresh, MD, PhD; Nick Patterson, PhD; Arti
Tandon; Neil R. Powe, MD, MPH; Nancy E.
Fink, MPH; John H. Sadler, MD; Matthew R.
Weir, MD; Hanna E. Abboud, MD; Sharon Adler,
MD; Jasmin Divers, PhD; Sudha K. Iyengar,
PhD; Barry I. Freedman, MD; Paul L. Kimmel,
MD; William C. Knowler, MD, DrPH; Orly F.
Kohn, MD; Kristopher Kramp, MS; David J.
Leehey, MD; Susanne Nicholas, MD, PhD;
Madeleine Pahl, MD; Jeffrey R. Schelling,
MD; John R. Sedor, MD; Denyse Thornly-Brown,
MD; Cheryl A. Winkler, PhD; and Michael W.
Smith, PhD.
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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