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Lupus in women: New genetic risk factors identified
Date:1/20/2008

Montreal, January 20, 2008 An international consortium of clinical scientists and genomics experts, including researchers from the Montreal Heart Institute (MHI) and Universit de Montral (UdeM), have uncovered multiple new genetic risk factors for systemic lupus erythematosus (SLE), commonly known as lupus. The large-scale genomic study is the first of its kind to investigate the genetic basis of lupus. Dr. John D. Rioux, associate professor of medicine at the MHI and UdeM, co-authored the study that appears in the January 20 online edition of Nature Genetics.

Systemic lupus can affect 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 one another and the environment.

The research team 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, 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.

Thanks to this discovery, we can now focus our research on the specific biological pathways and genes identified and dissect the precise molecular mechanisms by which these genes contribute to the risk for lupus, added Dr. Rioux.

This latest find comes 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 Universit de Montral. Dr. Tardif also mentioned that this remarkable contribution to the advancement of medical knowledge confirms the value of Universit de Montrals 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.


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Contact: Doris Prince
doris.prince@icm-mhi.org
51-437-633-303-074
University of Montreal
Source:Eurekalert

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