Lupus in Women: New Genetic Risk Factors Identified

An international consortium of clinical scientists and genomics experts, including researchers from the Montreal Heart Institute (MHI) and Université de Montréal (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.