Knowledge of the genetic influence on the molecular mechanisms and pathways that may cause psoriasis is useful in the prevention and treatment of the condition, particularly in the identification of potential drug targets.

It is generally accepted by medical researchers that a hereditary component of psoriasis exists, as approximately 1 in 3 patients with the condition has a close family member that also suffers from the condition. At present, it is believed that both genetic susceptibility and environmental factors are important in the development of psoriasis.

There are many gene mutations that may be involved in the pathology of psoriasis and research in this area is continuing to discover more about the mechanisms and contribution of the genes on the immune system and inflammatory response of the body.  This is discussed in more detail below.

Genetic Loci

Analysis of the classic genome-wide linkage has been able to identify genetic loci of chromosomes that are linked to psoriasis, which are referred to as psoriasis susceptibility. These include:

• PSORS1 (30-50% of cases of psoriasis)
• PSORS2
• PSORS3
• PSORS4
• PSORS5
• PSORS6
• PSORS7
• PSORS8
• PSORS9

Each of these loci is responsible for a significant part of the inflammatory response pathway in humans. Mutations in these genes are commonly found in patients that suffer from psoriasis.

PSORS1

The PSORS1 locus is particularly significant in the development of the condition as is believed to account for up to half of all psoriasis cases due to genetic susceptibility.  It is located on chromosome 6 in the major histocompatibility complex (MHC) and is responsible for the response of the immune system and encoding skin proteins associated with psoriasis.

There are three genes in this locus that have been identified be strongly associated with psoriasis vulgaris, including:

• HLA-C, variant HLA-Cw6: encodes MHC class 1 protein
• CCHCR1, variant WWC: encodes overexpressed coiled protein
• CDSN, variant allele 5: encodes overexpressed corneodesmosin protein

Interleukin Genes

Both the interleukin-12 subunit beta (IL12B) and IL23R are being investigated for their involvement in the pathology of psoriasis, due to their strong association with the condition. They are both on the up-regulation pathway for the gene for inflammation, tumor necrosis factor-α and nuclear factor KB.

IL12B exists on chromosome 5q and is linked to the expression of interleukin-12B. IL23R is on chromosome 1p and expresses the interleukin-23 receptor, which plays a role in the differentiation of T cells and their involvement in the inflammatory processes that cause psoriasis.

Other Gene Mutations

Identification of other gene mutations that may be involved in causing variants of psoriasis have been identified with genome-wide association scans. The mechanism of these genes in the pathology of the condition varies and is not completely understood, but may affect the signaling proteins for inflammation.

A mutation in the gene that is responsible for encoding the CARD14 protein has been identified as a cause of psoriasis, when in combination with an environmental trigger. This gene mutation can lead to the symptoms of the most common type of psoriasis, plaque psoriasis.

References

• https://www.psoriasis.org/research/genes-and-psoriatic-disease
• http://hmg.oxfordjournals.org/content/7/10/1537.full
• http://hmg.oxfordjournals.org/content/13/suppl_1/R43.full
• http://ard.bmj.com/content/64/suppl_2/ii37.full
• http://www.bmj.com/content/333/7564/380

Further Reading

• All Psoriasis Content
• What is Psoriasis?
• Psoriasis Types
• Psoriasis Treatment
• Psoriasis Topical Treatment

Written by

Yolanda Smith

Yolanda graduated with a Bachelor of Pharmacy at the University of South Australia and has experience working in both Australia and Italy. She is passionate about how medicine, diet and lifestyle affect our health and enjoys helping people understand this. In her spare time she loves to explore the world and learn about new cultures and languages.