PRESS RELEASE
RESEARCHERS FROM THE CENTRE FOR GENOMIC REGULATION IN BARCELONA (CRG) IDENTIFIED A MAJOR GENE RESPONSIBLE FOR PSORIASIS
This research, published online in the journal Nature Genetics, has shown that the absence of the LCE3B and LCE3C genes contributes to over 20% the risk of developing psoriasis, becoming the main genetic factor of susceptibility after the HLA locus.
Researchers studied samples from more than 2,500 subjects of Spain, Holland, Italy and the United States.
Psoriasis is a chronic inflammatory disease of the skin, affecting over 15 million people in Europe, and usually appearing between the 15 and 40 years of age. The disease is due to a combination of genetic and environmental factors. Some drugs, infection, trauma, cold weather and stress are the main triggers of this skin disease, characterized by the presence of more or less extensive injuries in the skin but also affecting joints.
The specific cause of psoriasis is unknown. In psoriasis there is abnormal proliferation and differentiation (excessive growth) of skin cells, due to changes in the skin, specifically the keratinocytes. Among the changes that have been described in this disease there is an abnormal reaction of the cells of the immune system.
Psoriasis is most common among identical twins (monozygotic) and there are families in which psoriasis is highly prevalent. Although scientists have identified some genetic factors involved in the susceptibility to psoriasis (the major histocompatibility, or HLA, being the main one), few genetic factors are common to many people, probably reflecting the exposure of humans to different environments.
Investigators of the Centre for Genomic Regulation in Barcelona (CRG) have studied samples of patients and samples from control subjects in a comprehensive study of the genome. Researchers have explored regions of the genome that vary in the number of copies of the genes they contain, known as CNV (copy number variants). The investigation has led to determine that patients with psoriasis lack, with a significantly high frequency, the two copies of two genes, known as LCE3B and LCE3C. These genes play an important role in the formation of a functional epidermis. Researchers studied samples from more than 2,500 subjects of Spain, Holland, Italy and the United States, obtaining similar results in all groups. The absence of the LCE3B and LCE3C genes contributes to over 20% the risk of developing psoriasis, becoming the main genetic factor of susceptibility after the HLA locus.
This research has shown that the LCE3B and LCE3C genes, which are part of a complex organization of genes in human chromosome 1 (Epidermal Differentiation Gene Complex), are expressed in the skin of psoriasis patients, indicating an abnormal regulation in the expression of proteins that have a key role during the growth process of the epidermis.
The research, led by Xavier Estivill, Coordinator of the Genes and Disease Program at the CRG, was published online in the journal Nature Genetics and gathers a group of investigators from different countries (Italy, United Kingdom, Netherlands and United States).
This investigation is a milestone in the identification of genes involved in multifactorial diseases. CRG investigators Rafael de Cid and Eva Riveira have had a major role in developing the work, which has count on many clinical collaborators. Researchers are now studying other processes that alter the entry barrier for microorganisms and other agents that can damage the skin and other tissues, for which these genes may have a protective role.
The work has immediate diagnostic implications and opens new avenues to explore preventive and curative treatments for a disease that affects 2% of people and for which only palliative treatments are available.
This research was supported by the “Generalitat de Catalunya”, the Ministry of Science and Innovation, and the European Commission. These results represent an advance in the implementation of the genome sequencing of various diseases, for which Spain has decided to play an important role by creating a new sequencing centre and financing projects in this field of knowledge.
Reference work: De Cid, R. et al.: “Deletion of the late cornified envelope LCE3B and LCE3C genes as a susceptibility factor for psoriasis”. Publishing in Nature Genetics, DOI: 10.1038/ng.313.
For more information: Laia Cendrós, Communication & PR Dept., Centre for Genomic Regulation (CRG), Dr. Aiguader, 88 – Edif. PRBB, 08003 Barcelona, Spain, Tel. +34 93 316 02 37, comunicacio@crg.es