Genetic polymorphisms associated with psoriasis and development of psoriatic arthritis in patients with psoriasis

PLoS One. 2018 Feb 1;13(2):e0192010. doi: 10.1371/journal.pone.0192010. eCollection 2018.

Abstract

Background: Psoriasis (PsO) is a chronic inflammatory disease with predominantly cutaneous manifestations. Approximately one third of patients with PsO develop psoriatic arthritis (PsA), whereas the remaining proportion of patients has isolated cutaneous psoriasis (PsC). These two phenotypes share common immunology, but with different heredity that might in part be explained by genetic variables.

Methods: Using a candidate gene approach, we studied 53 single nucleotide polymorphisms (SNPs) in 37 genes that regulate inflammation. In total, we assessed 480 patients with PsO from DERMBIO, of whom 151 had PsC for 10 years or more (PsC10), 459 patients with PsA from DANBIO, and 795 healthy controls. Using logistic regression analysis, crude and adjusted for age and gender, we assessed associations between genetic variants and PsO, PsC10, and PsA, as well as associations between genetic variants and development of PsA in PsO.

Results: Eleven polymorphisms in 10 genes were nominally associated with PsO and/or PsC and/or PsA (P < 0.05). After correction for multiple testing with a false discovery rate of 5%, two SNPs remained significant: TNF (rs361525) was associated with PsO, PsC10, and PsA; and IL12B (rs6887695) was associated with PsO.

Conclusion: Among a cohort of Danish patients with moderate-to-severe psoriasis, two SNPs in the IL12B and TNF genes were associated with susceptibility of psoriasis. None of the SNPs were specifically associated with isolated cutaneous psoriasis or psoriatic arthritis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arthritis, Psoriatic / complications*
  • Denmark
  • Genetic Predisposition to Disease
  • Humans
  • Polymorphism, Single Nucleotide*
  • Psoriasis / complications
  • Psoriasis / genetics*

Grants and funding

The work was funded by Psoriasisforeningen, Robert Wehnerts og Kirsten Wehnerts Fonden, Knud og Edith Eriksens Mindefond, Gigtforeningen (A2037, A3570), DERMBIO, and the Novo Nordisk Foundation (NNF15OC0017622). The Novo Nordisk Foundation provided support in form of a scholarship for author NDL, but did not have any role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The rest of the Funders supported the study with funding for collection and analysis of biological material. MKA is employed by Zitelap Aps. Zitelap Aps provided support in the form of salary for author MKA and is responsible for management of the DERMBIO and DANBIO databases, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific role of this author is articulated in the ‘author contributions’ section.