A North-American study reveals a new genetic risk factor for the millions
of people with SLE and RA
MONTREAL and TORONTO, Aug. 1 /CNW Telbec/ - A North-American consortium
of clinical scientists and genomics experts, including major contributions
from Canadian researchers - Dr. John D. Rioux from the Montreal Heart
Institute and Université de Montréal and Drs. Joan Wither and Paul R. Fortin
from the University Health Network in Toronto - have identified a novel
genetic risk factor for systemic lupus erythematosus (SLE); a disease commonly
known as "lupus". Lupus is a chronic "autoimmune" disease in which the body's
immune system attacks healthy tissues and organs. Symptoms range from skin
rashes and joint pain to strokes, seizures and organ failure. This study shows
that genetic variation of a particular gene -- known as TNFAIP3 -- leads to
SLE and Rheumatoid Arthritis (RA). This study also confirmed the identity of
an additional four genetic risk factors for SLE: the HLA, IRF5, BLK and STAT4
genes. These findings appear in the August 1st online edition of Nature
In order to complete this study, the researchers examined the more than
20,000 genes in the human genome by performing over 300,000 genetic tests of
DNA samples from 431 patients with SLE and compared the results to those of
2155 healthy individuals. These results were then confirmed in a group of
740 SLE patients and their family members. In healthy individuals, when a
virus or bacteria enters a human body, the immune system revs up to fight and
expel the invader. Once the invader is gone, the body puts on the brakes to
stop the immune response. In lupus patients it is believed that the immune
system keeps going at full speed long after the threat is gone, causing damage
to the body. "TNFAIP3 can be thought of as a critical brake mechanism for the
immune system," said Patrick M. Gaffney, the senior author of the study and
Associate Member of Oklahoma Medical Research Foundation's Arthritis and
Immunology Research Program.
"It has been suspected for a long time that problems in the regulation of
the immune system lead to lupus. The identification of TNFAIP3 and the other
genetic risk factors now indicate the specific biological pathways that need
to be targeted in order to generate better diagnostic markers and effective
therapies." says Dr. John D. Rioux, Ph.D., Associate Professor of Medicine at
the Montreal Heart Institute (MHI) and Université de Montréal, and one of the
"I am excited that our Canadian cohort has revealed its full potential
for the identification of important new SLE genes," says Dr. Paul R. Fortin,
co-principal investigator of the CIHR-funded CaNIOS Genetic and Environment
SLE (GenES) study and Professor of Medicine at the University Health Network
Research Institute and the University of Toronto.
"The observation that genetic variation in TNFAIP3 is associated with
both SLE and Rheumatoid Arthritis suggests that some of the risk factors for
these two conditions are shared," says Dr. Joan E. Wither, co-principal
investigator of the GenES study and Associate Professor of Medicine and
Immunology at the University of Toronto.
Systemic lupus can involve the joints, kidneys, heart, lungs, brain and
blood. The disease occurs in about 31 out of every 100,000 people and affects
women nine times more frequently than men. Scientists believe that lupus is
caused by genetic variants that interact with each other and the environment.
About the Montreal Heart Institute: www.icm-mhi.org.
About the Université de Montréal: www.umontreal.ca.
About Canadian Network for Improved Outcomes in SLE: www.canios.ca.
Genetic Variants Near TNFAIP3 on 6q23 are Associated with Systemic Lupus
Authors of this study are: Robert R. Graham, Chris Cotsapas, Leela
Davies, Rachel Hackett, Christopher J. Lessard, Joanlise M. Leon, Noel P.
Burtt, Candace Guiducci, Melissa Parkin, Casey Gates, Robert M. Plenge,
Timothy W. Behrens, Joan E. Wither, John D. Rioux, Paul R. Fortin, Deborah
Cunninghame Graham, Andrew K. Wong, Timothy J. Vyse, Mark J. Daly, David
Altshuler, Kathy L. Moser and Patrick M. Gaffney.
Nature Genetics, online August 1st, 2008
For further information:
For further information: Johanne Carrier, Communications and Public
Relations, Montreal Heart Institute, (514) 591-0502, (514) 751-9983