More complete genetic map of scleroderma disease makes more effective medications possible

Scientists at the University of Granada and the Spanish National Research Council (CSIC) carried out the largest study to date of the disease with a sample of more than 5000 affected patients.

On Monday, 29 February organizers promoted Rare Disease Day under the slogan "Join us in making the voice of rare diseases heard."

Scientists from the University of Granada and the Institute of Parasitology and Biomedicine "López-Neyra" (CSIC) have succeeded in creating the most complete genetic map to date of systemic sclerosis, or scleroderma, a rare disease that affects approximately one out of every 10,000 people in Europe and North America.

Their research opens doors in the field of targeted treatment and the development of personalized medicine for patients suffering from the disease. It may also contribute to early diagnosis and prevention.

Scleroderma primarily attacks middle-aged women and causes death in a high percentage of cases. It is an autoimmune disease characterized by an imbalance in which the patient's own immune system attacks the connective tissues causing generalized fibrosis, which is the principle symptom of the disease.

In spite of a high degree of heterogeneity in the clinical presentation of the disease, its early signs are usually Raynaud's phenomenon (the whitening and restricted blood flow to the fingers) and harm to blood capillaries. This can end up leading to digital sores and, on occasion, amputation of the phalanges.

Nevertheless, the primary complication of the disease currently is its affect on the lungs and the onset of pulmonary hypertension, which can drastically reduce the patient's life expectancy. Scleroderma figures among the complex diseases as its emergence is due to environmental factors (unknown until now) as well as genetic predisposition.

Study of more than 5000 affected patients

In the study, the authors (under the direction of Javier Martín of the Institute of Parasitology and Biomedicine "López-Neyra") analysed the genetic component of the disease in order to help in its diagnosis and contribute to an increased knowledge of the processes it involves. In spite of the rareness of scleroderma, they were able to bring together a group of 5000 patients and more than 8000 non-affected control subjects thanks to the collaboration of hospitals from all over Spain, Europe and North America.

The main author of the study, Lara Bossini Castillo, led the bioinformatics analysis of the first study based on a new genotype platform, known as ImmunoChip, in patients with scleroderma.

"The ImmunoChip was designed to explore in depth the genetic regions involved in immune system diseases. Its use in the study of scleroderma allowed us to identify 3 new genes involved in the development of the disease and to include new procedures with regard to its biology," the researcher explained.

The study has also determined possible genetic associations of the different subtypes of the disease, especially the more aggressive ones, such as the effect on the lungs mentioned above. "In that sense, we confirmed the association of a haplotype [a set of genetic variants] of the CD226 gene with an increase in the risk of the onset of pulmonary fibrosis in patients" she explained.

Bossini currently works at the Wellcome Trust Sanger Institute (Hinxton, Cambridge), a world leader in the study of the human genome, diseases and biomedicine.