Scientists believe that both environmental and genetic factors contribute to the development of psoriasis. Psoriasis is an inflammatory skin disease that causes skin cells to grow at an abnormally fast rate. Psoriasis is considered an autoimmune disease, and it affects about 2 percent to 3 percent of the world’s population. Known environmental factors and triggers — such as smoking, specific infections, and obesity — are associated with the development of psoriasis, but they don’t tell the whole story. So where do genes come in?
Being knowledgeable about the genetics involved with psoriasis can help someone gain a better understanding of the disease, why it occurs, and why certain treatment approaches may work. The genetics of any disease can be very complicated, but as they learn more, experts may develop better treatment options for prevention and intervention.
There is not a clear pattern of inheritance associated with psoriasis, although it seems to run in some families. Studies have revealed that if both parents have psoriasis, their child has a 65 percent chance of developing the condition. The risk of someone developing psoriasis drops down to 28 percent if only one parent has the disease.
Studies of identical twins have also shed some light on the genetic basis of psoriasis. Identical twins share nearly all the same genetic material. Therefore, if one twin developed psoriasis, and the disease was based on a completely genetic cause, it would be expected that the other twin would have a nearly 100 percent chance of developing psoriasis. This pattern is not observed between identical twins with psoriasis, however. Instead, twin studies suggest that if one twin has psoriasis, the other twin has a 35 percent to 72 percent chance of developing psoriasis. These findings suggest that genes may make psoriasis more likely, but they are not wholly responsible for the development of psoriasis.
Scientists have identified what they call psoriasis susceptibility loci, which refer to a collection of genes associated with the development of psoriasis. One of these loci, called the PSORS1 locus, has been consistently identified and replicated by other studies.
The PSORS1 locus is found in the major histocompatibility complex (MHC) area of the genome (the entire genetic code). The MHC genes code for proteins known as human leukocyte antigens (HLAs), which typically help the immune system recognize and attack foreign invaders. However, some evidence suggests certain HLAs may activate T cells (immune cells) to attack the body’s own tissues.
One of the most relevant HLA genes implicated in the development of psoriasis is HLA-Cw6, located in the PSORS1 locus. Studies have demonstrated that about 46 percent of people with plaque psoriasis carry the HLA-Cw6 gene, compared to only 7.4 percent of the general population. Having the HLA-Cw6 gene is not sufficient to drive disease on its own.
The HLA-Cw6 gene and the PSORS1 locus have also been implicated in the development of psoriatic arthritis.
Genome-wide association studies (GWAS) scan the genetic material of people with and without psoriasis to identify variations in the genetic code that may be associated with the disease.
GWAS have identified several gene variations associated with inflammation, the immune system, and the risk of developing psoriasis, such as:
Many of these cytokines (inflammatory markers) and inflammatory signaling pathways involved with psoriasis can accelerate the growth of keratinocytes (skin cells). They can also affect the activity of immune cells. These genes have also been implicated in the development of psoriatic arthritis.
In addition to GWAS, the results of biologic treatment support the idea that cytokines such as TNF-α, IL-17A, and IL-23 are involved in the development of psoriasis. Several biologics have now been developed to target and block TNF-α, IL-17A, or IL-23 for the treatment of psoriasis and psoriatic arthritis.
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