Genetics behind the disease systemic lupus erythematosus almost completed

A new study has mapped the risk factors behind the autoimmune disease SLE in the entire human genome.

The findings of the study, in which researchers from Uppsala University took part, are being presented today in the Web edition of The New England Review of Medicine.

The study charts which of the human being’s some 20,000 are the strongest risk factors for SLE (systemic lupus erythematosus). The analysis was performed with half a million genetic markers, so-called SNP markers, that are evenly distributed across the whole genome. Two research teams from Uppsala University, Ann-Christine Syvänen’s and Lars Rönnblom’s groups at the Department of Medical Sciences, were part of the group behind the study, which was led by scientists from the U.S. The study included 800 Swedish SLE patients from rheumatology clinics at Akademiska Hospital in Uppsala, Karolinska Hospital in Stockholm, and the university hospitals in Umeå and Lund.

“The study is especially interesting since SLE is seen as a model disease for autoimmune disorders, where the body’s immune defense attacks the patient’s own tissue,” says Lars Rönnblom, professor of rheumatology.

In SLE most body organs can be damaged by the autoimmune process. From studies of twins we know that SLE has strong genetic connections where the interaction with environmental factors can lead to the genesis of the disease. With the findings of this new study, researchers can now move on to functional and clinical analyses. Functional analyses can figure out the molecular mechanisms in SLE, which ultimately can lead to better drugs for the disease.

“Since SLE is characterized by many different pathological symptoms, these genetic findings can also lead to genetic tests in the future to make it possible to classify the disease in each individual more exactly, thereby providing support for treatment decisions,” says Ann-Christine Syvänen, professor of molecular medicine.

The new study identifies two previously unknown genes, BLK and ITGAM, with functions in the immune system’s cells, as risk factors for SLE. Moreover, the study identifies two previously known genes from the interferon system, IRF5 and STAT4, and the well-known HLA system as the three strongest risk factors for SLE. These same Uppsala scientists originally identified the IRF5 gene as a risk factor, in 2005.

The genetic analyses of the Swedish patients were done at the SNP genotyping laboratory at Akademiska University Hospital in Uppsala. It became possible only in 2007 to perform genetic analyses on a scale comprising the entire genome, thanks to extremely rapid technological development.

“The advantage of genetic studies across the entire genome is that they unconditionally lead to the identification of all the genes that contribute to the genetic risk for SLE,” says Ann-Christine Syvänen.