Discoveries reveal new genetic risk factors
for the millions of people with lupus
MONTREAL, Jan. 20 /CNW Telbec/ - An international consortium of clinical
scientists and genomics experts, which includes the Montreal Heart Institute,
conducted a large-scale genomic study that uncovered multiple new genetic risk
factors for systemic lupus erythematosus (SLE), commonly known as lupus. The
study is the first comprehensive one of its kind investigating the genetic
basis of lupus. These findings appear in the January 20 online edition of
Nature Genetics. Dr. John D. Rioux, Ph.D., Associate Professor of Medicine at
the Montreal Heart Institute (MHI) and the Université de Montréal, is one of
the study's authors.
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.
The researchers studied the DNA of 720 women of European descent with
lupus and 2,337 women without lupus. They scanned the entire genome for more
than 317,000 single nucleotide polymorphisms (SNPs), which are locations on
chromosomes where a single unit of DNA, or genetic material, may vary from one
person to the next. The goal was to identify SNPs linked to lupus. They
confirmed these results in another independent set of 1,846 women with lupus
and 1,825 women without lupus.
The scientists found evidence of an association to three genes: ITGAM,
KIAA1542 and PXK, and to a region of the genome that does not contain any
known genes. ITGAM is important for both the adherence of immune cells and for
cleaning up pathogens. KIAA1542 is important for translating the DNA code into
proteins. PXK encodes a molecule that transmits signals and controls complex
processes in cells. The scientists also found association in genes previously
associated with lupus and other autoimmune diseases.
"These results help to delineate the genetic distinctions between
rheumatoid arthritis, lupus and other autoimmune diseases, which could lead to
earlier, more accurate diagnoses," said Dr. John Harley, M.D., Ph.D., lead
author and SLEGEN director, from the Oklahoma Medical Research Foundation.
"They identify biologic pathways that help us understand the condition better
and suggest additional genetic and non-genetic triggers."
"These will now allow us to focus our research on the specific biological
pathways and genes identified in this study and to dissect the precise
molecular mechanisms by which these genes contribute to the risk for lupus,"
added Dr. John D. Rioux.
In fact, these discoveries come only a few weeks following the
identification of one of the first genetic risk factors for systemic lupus,
published in the January 2008 issue of Nature Genetics. "In our previous
study, we identified that a gene called TNFSF4, important for the
communication between different cells of the immune system, is also involved
in the susceptibility to systemic lupus," said Dr. Rioux. "The technological
advances that made these studies possible are truly revolutionizing our
ability to identify genetic risk factors for common diseases and these
discoveries represent a major advance in our efforts to use genetic
information to improve on the diagnosis and treatment of our patients,"
concluded Dr. Jean-Claude Tardif, Director of the Research Center of the MHI
and Professor of Medicine at the MHI and the Université de Montréal.
Dr. Tardif also mentioned that "this remarkable contribution to the
advancement of medical knowledge confirms the value of Université de
Montréal's strategy in the field of genetics and genomics, which is based upon
targeting important medical questions, supporting world class researchers and
their international collaborations, in order to have a significant impact on
our health system and on the scientific, social and economic development of
Quebec and Canada".
This work was supported by the Alliance for Lupus Research and the
National Institutes of Health of the United States.
About Dr. John D. Rioux
Dr. Rioux, Ph.D., is an Associate Professor of Medicine at the Université
de Montréal and at the MHI where he works as a researcher and director of the
Laboratory in Genetics and Genomic Medicine of Inflammation
(www.inflammgen.org). He is also a visiting scientist at the Broad Institute
of MIT and Harvard, and holder of the Canada Research Chair in Genetics and
Genomic Medicine of Inflammation.
About the Montreal Heart Institute
Founded in 1954, the Montreal Heart Institute constantly aims for the
highest standards of excellence in the cardiovascular field through its
leadership in prevention, ultra-specialized care, training of professionals,
clinical and fundamental research, and assessment of new technologies. It is
affiliated with the Université de Montréal and its clinical outcomes are among
the best in the world.
The MHI Research Centre officially came into existence in 1976 and has
made enormous strides since its creation. Today, there are approximately
500 employees, students and researchers at the MHI Research Centre. The MHI's
outstanding feature is the balance it achieves between basic research,
clinical research and clinical care. Its prime focus areas of research are
vascular diseases, myocardial function and electrophysiology. MHI researchers
also contribute to the advancement of knowledge and medical applications in
the fields of genomics (in particular in disease gene discovery and
pharmacogenomics), biomarkers and preventive cardiology. To learn more about
the Institute, please visit our website at www.icm-mhi.org.
About the Université de Montréal
Deeply rooted in Montreal and dedicated to its international mission, the
Université de Montréal is one of the top universities in the world,
particularly in the French-speaking world. Founded in 1878, the Université de
Montréal today has 13 faculties and together with its two affiliated schools,
HEC Montréal and Ecole Polytechnique, constitutes the largest centre of higher
education and research in Québec, the second largest in Canada, and one of the
major centres in North America. It brings together 2,500 professors and
researchers, accommodates more than 55,000 students, offers some 650 programs
at all academic levels, and awards about 3,000 masters and doctorate diplomas
Genome-wide association scan in women with systemic lupus erythematosus
identifies susceptibility variants in ITGAM, PXK, KIAA1542 and other loci
The International Consortium for Systemic Lupus Erythematosus Genetics
Authors of this tudy are : John B Harley, Marta E Alarcon-Riquelme,
Lindsey A Criswell, Chaim O Jacob, Robert P Kimberly, Kathy L Moser, Betty P
Tsao, Timothy J Vyse & Carl D Langefeld, and Swapan K Nath, Joel M Guthridge,
Beth L Cobb, Daniel B Mirel, Miranda C Marion, Adrienne H Williams, Jasmin
Divers, Wei Wang, Summer G Frank, Bahram Namjou, Stacey B Gabriel, Annette T
Lee, Peter K Gregersen, Timothy W Behrens,, Kimberly E Taylor, Michelle
Fernando, Raphael Zidovetzki, Patrick M Gaffney,, Jeffrey C Edberg, John D
Rioux, Joshua O Ojwang, Judith A James, Joan T Merrill, Gary S Gilkeson,
Michael F Seldin, Hong Yin, Emily C Baechler, Quan-Zhen Li, Edward K Wakeland,
Gail R Bruner, Kenneth M Kaufman, & Jennifer A Kelly
Nature Genetics, online January 20th 2008
Polymorphism at the TNF superfamily gene TNFSF4 confers susceptibility to
systemic lupus erythematosus
Deborah S Cunninghame Graham, Robert R Graham, Harinder Manku, Andrew K
Wong,John C Whittaker, Patrick M Gaffney, Kathy L Moser, John D Rioux, David
Altshuler,Timothy W Behrens & Timothy J Vyse
Nature Genetics, January 2008
For further information:
For further information: Doris Prince, Head, Communications and Public
Relations, Montreal Heart Institute, (514) 376-3330, ext. 3800,
firstname.lastname@example.org; Dr. John D. Rioux and a patient are available for