Genetics of Psoriasis


Psoriasis is a chronic inflammatory skin disorder. Several studies suggested psoriasis to be a complex multifactorial genetic disease, but the exact triggering factor is yet to be determined. Many psoriasis susceptibility loci are located near genes that belong to immunologic pathways, indicating that defective immune system might play a major role in psoriasis pathogenesis. Human leukocyte antigen (HLA)‐Cw6 allele within the major histocompatibility complex (MHC) Class I region was found to be the most significantly associated allele. Several other genetic loci have been reported, but the risk assessed by these factors is variable across populations. Epistatic interactions between HLA‐Cw6 and other susceptibility loci have also been demonstrated in some populations. Furthermore, recent studies have suggested the association of several genetic markers with the drug response. Genetic studies are thus important not only to identify markers for disease predisposition and pathogenesis but also to predict drug response and develop personalised medications.

Key Concepts

  • Psoriasis is a common chronic inflammatory disease characterised by hyper‐proliferating keratinocytes, with varying prevalence among different populations worldwide.
  • Population‐, family‐ and twin‐based studies have indicated a genetic predisposition in psoriasis; however, they cannot fully explain the disease pathogenesis.
  • Many of the strongly associated loci with psoriasis are also associated with the immune system.
  • HLA‐Cw6 allele is the most important risk allele within the MHC Class I region.
  • Several genetic susceptibility loci show differential associations between ethnic populations, suggesting potential genetic heterogeneity of psoriasis across diverse ancestries.
  • Population‐specific genetic association studies are essential to elucidate the actual causal variants and develop more targeted therapeutics.
  • The impact of genetic polymorphisms on the response to drugs has been demonstrated in psoriasis.
  • Development of such targeted treatment based on patients' genetic background (pharmacogenetics) is a prospective area for disease management in psoriasis.

Keywords: psoriasis vulgaris; genetic markers; single‐nucleotide polymorphism; genome‐wide association studies; major histocompatibility complex; HLA‐Cw6; immunogenetics; pharmacogenetics; cyclosporine A; ustekinumab

Figure 1. The fundamental role of genetics in psoriasis pathogenesis.
Figure 2. Generalised schematic representation of genetic variations within certain causal genes might affect response to a particular drug. A few of the specific responses have been shown here briefly. This observation inspired the need to study patients' genetic background before prescribing the drugs. A detailed list is presented in Table .


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Further Reading

Boehncke WH and Schon MP (2015) Psoriasis. Lancet 386: 983–994.

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Capon F, Trembath RC and Barker JN (2004) An update on the genetics of psoriasis. Dermatologic Clinics 22: 339–347.

Foulkes AC and Warren RB (2015) Pharmacogenomics and the resulting impact on psoriasis therapies. Dermatologic Clinics 33: 149–160.

Harden JL, Krueger JG and Bowcock AM (2015) The immunogenetics of psoriasis: a comprehensive review. Journal of Autoimmunity 64: 66–73.

Nair RP, Stuart P, Henseler T, et al. (2000) Localization of psoriasis‐susceptibility locus PSORS1 to a 60‐kb interval telomeric to HLA‐C. American Journal of Human Genetics 66: 1833–1844.

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Okada Y, Han B and Tsoi LC (2014) Fine mapping major histocompatibility complex associations in psoriasis and its clinical subtypes. American Journal of Human Genetics 95: 162–172.

Prieto‐Perez R, Cabaleiro T, Dauden E, et al. (2013) Genetics of psoriasis and pharmacogenetics of biological drugs. Autoimmune Diseases 2013: 613086.

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Das, Anamika, Chandra, Aditi, Lahiri, Anirudhya, Datta, Shalini, Senapati, Swapan, and Chatterjee, Raghunath(Sep 2016) Genetics of Psoriasis. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0025041]