Affecting approximately 125 million people globally, the World Health Organisation views psoriasis as a non-contagious disease of public health concern due to its increasing prevalence. Numerous studies are exploring the role of genetics in the onset of this disease, but what is the actual situation?
Psoriasis in a nutshell.
The psoriasis is a chronic skin disease characterised by the presence of red patches covered with scales, which can sometimes itch. The presence of dead cells at the lesion sites, similar to powder, is very characteristic of psoriasis. The lesions are usually found in areas of friction (elbows, forearms, knees, legs), but nails and the scalp are also common locations. Moreover, psoriasis is not limited to the skin as it can manifest in the joints, referred to as psoriatic arthritis.
Regarded as an inflammatory disease, psoriasis is the result of an immune system malfunction. For reasons still unknown, immune cells secrete inflammatory molecules into the skin. These molecules stimulate the proliferation of keratinocytes which accumulate on the skin's surface: this is known as hyperkeratosis.
Due to the poor understanding of this disease, individuals suffering from psoriasis are subject to stigmatisation , leading to social isolation. Therefore, the risk of anxiety and depression is significantly high. Psoriasis is a dermatosis that appears in flare-ups. It occurs in individuals with a genetic predisposition and under the influence of certain factors.
Psoriasis: A Genetic Component.
At least 30% of psoriasis cases correspond to family forms (presence of family history) involving a genetic predisposition. Indeed, there is not a single gene responsible for psoriasis disease but rather a set of genes. The genetic variants associated with psoriasis disease are located in the genes involved in immunity, which is the cause of an immune system disorder.
To note : in the case of familial forms, if one of the two parents is affected, the risk for the child to suffer from the disease varies from 5 to 10%.
According to genetic linkage studies, PSORS1 is the primary locus of psoriasis susceptibility: it is responsible for 35 to 50% of psoriasis heritability. The PSORS1 region also contains the CDSN gene which codes for the corneodesmosin, a desmosomal protein involved in the cohesion and desquamation of keratinocytes. The locus is associated with an early onset of the disease.
The other loci highlighted by genetic linkage studies are PSORS2 and PSORS4. The most probable susceptibility gene in PSORS2 is CARD14. It codes for an activator of the nuclear factor-κB (NF-κB) and contains variants associated with both rare and common forms of psoriasis. As for the PSORS4 locus, it contains the genes of the "late cornified envelope" (LCE), which code for proteins of the horny layer involved in terminal epidermal differentiation.
Thanks to scientific advancements, various genetic analysis methods such as GWAS (Genome Wide Association Study) or CGH Microarray, over 80 loci have been associated with a high risk of psoriasis.
Thus, psoriasis is a disease for which genetic factors account for 70% of the disease's susceptibility. Understanding the genetic aspect of psoriasis is crucial, as it enables the development of effective treatments.
BARKER J.N & al. Psoriasis and genetics advances in dermatology and venereology (2020).
OKADA Y. The current landscape of psoriasis genetics in 2020. Journal Pre-Proof (2020).