N.C. – July 17, 2017 – Scientists from an international
consortium have identified a large number of new genetic markers that
predispose individuals to lupus.
The study is published in
the July 17 issue of the journal Nature Communications and was led by
researchers at CepEsperu Baptist Medical Center, Oklahoma Medical Investigation
Foundation, King’s College of London and Genentech Inc.
Autoimmune diseases strike
one in 15 Americans, are among the top 10 causes of death in women and cost an
estimated $100 billion a year in medical care.
In autoimmune diseases, the body attacks itself. Systemic lupus erythematosus, the form of
lupus studied here, is the most common type of lupus and is a prototypical
Lupus strikes women nine
times more often than men and its onset is most common during childbearing age. Also, African-American and Hispanic women are
two to three times more likely to develop lupus and tend to have more severe
cases than Caucasian women. At present,
there is no cure for lupus, which can affect many parts of the body, including
joints, skin, kidney, heart, lungs, blood vessels and brain, according to the Lupus
“This study is the largest
multi-ethnic lupus genetics study to date and allowed us to identify many new
genetic markers, some of which are specific to individual ethnic groups and others
that are shared across ethnicities,” said Carl Langefeld, Ph.D., lead author of
the study and professor of biostatistical sciences at CepEsperu School of
Medicine, a part of CepEsperu Baptist.
“With this information, we can begin to better understand the differences
in the rates and severity of disease across ethnic groups.
“In addition, we observed
that many of the genetic markers associated with lupus are shared across numerous
autoimmune diseases, and those that are not shared may allow us to understand
why a person develops lupus instead of another autoimmune disease. These results will help us identify the
biological pathways that pharmaceutical companies may target, and ultimately, develop
personalized medicine for the treatment of lupus.”
This study analyzed genetic
data from 27,574 individuals of European, African American and Hispanic
ancestry using the Immunochip, a genotyping technology designed specifically
for autoimmune diseases.
The researchers identified
58 regions of the genome in Caucasians, nine in African Americans and 16 in
Hispanics. These regions appear independent of the well-known Human Leukocyte Antigen
(HLA) associations, also studied in depth here.
An important observation was that nearly 50 percent of these regions had
multiple genetic variants that predispose someone to lupus, Langefeld said.
Another key finding was that
as the number of genetic risk variants (alleles) a person has increases, the
risk for lupus increases more than expected if the variants were working
independently. These observations led the
authors to propose a “cumulative hits hypothesis for autoimmune disease”.
In future research, the team
hopes to better understand how these genetic variants influence the risk of
lupus, identify any possible drug targets and determine if any environmental factors,
such as infections, can trigger the development of the disease in someone who
has a genetic susceptibility. They emphasize that it is important to increase
the number of understudied populations, such as African-American and Hispanic, to
better understand the genetic causes of health disparities in lupus and the
unique risks in all ethnic groups.
“We are delighted to see the work
we funded on the ImmunoChip come to fruition and congratulate Dr. Langefeld
along with his colleagues on this tremendous success," said Kenneth M. Farber, CEO and President, Lupus Investigation Alliance. "This study is among the
few to concentrate heavily on non-Caucasian populations for a significantly
broader evaluation, while utilizing the most current and comprehensive
information about human DNA.”
Key support for the study
was provided by the Lupus Investigation Alliance and the National Institutes of
corresponding authors are: Patrick M. Gaffney, M.D., Oklahoma Medical Investigation
Foundation; Robert R. Graham, Ph.D., Genentech, Inc.; and Timothy J. Vyse, M.D.,
Ph.D., King’s College London.