New Hypotheses in the Genetics of Psoriasis and Other ‘Complex’ Diseases

Abstract

Psoriasis is a complex genetic disorder in which the disease, according to the current concept, is caused by the interplay of many different genes. However, recent genetic studies indicate that the location of these genes varies considerably among populations and families, raising the question of how the same phenotype can be induced by such variable genetic linkages. To circumvent these discrepancies we propose that psoriasis could be induced by the same repetitive DNA sequence, an endogenous retroviral element present at different locations in the genome. The occurrence of the disease could be linked to an abnormal activation of one or more endogenous retroviral element copies due to their location and/or to modification of their sequence. This unifying concept would simplify our understanding of genetically complex diseases.

Risk factors for psoriasis: A case–control study

“…Familial clustering in psoriasis patients (especially with guttate psoriasis) have been reported in several studies 10,13,14 . This has suggested a strong genetic susceptibility to psoriasis 4,15 . Approximately 40% of psoriatics have a family history of this disease among first‐degree relatives 16 .…”

“…The etiology of psoriasis appears to be multifactorial, but evidence suggests T‐lymphocyte‐based immunopathogenesis 2,3 . According to the current concept, psoriasis is a complex genetic disorder caused by the interplay of many different genes 4 . Some candidate genes like p53 are suspected of being involved in the pathogenesis of the disease 5 …”

“…2,3 According to the current concept, psoriasis is a complex genetic disorder caused by the interplay of many different genes. 4 Some candidate genes like p53 are suspected of being involved in the pathogenesis of the disease. 5 Although a genetic basis exists, environmental triggers exacerbate symptoms.…”

Pathophysiology of psoriasis

“…[13] Many authors classify psoriasis as a genetically complex disease as it shares features like the pattern of inheritance, environmental influence and immune dysregulation with diseases such as diabetes mellitus and Crohn's disease. [14] One school of thought is that psoriasis results from the interplay of multiple genes. The drawback of this hypothesis is that although the psoriasis susceptibility genes are located in numerous loci throughout the genome, these locations vary among different populations and families, and the results are difficult to replicate.…”

“…Goilhou et al hypothesize that the same genes may be present at these different loci as "jumping genes or retrotransposons". [14] This implies that a sequence may be present as multiple copies in the human genome and the disease manifests when one or several copies are activated. Human endogenous retroviruses (HERVs) may fit this criterion.…”