Gene Variant in the NF- κ B Pathway Inhibitor NFKBIA Distinguishes Patients with Psoriatic Arthritis within the Spectrum of Psoriatic Disease

Biomed Res Int. 2019 Nov 11:2019:1030256. doi: 10.1155/2019/1030256. eCollection 2019.

Abstract

Background and aims: The NF-κB pathway has been implicated in the genetic aetiology of psoriatic disease. However, since most patients with arthritis have psoriasis, discerning the genetic contributions to both aspects of psoriatic disease is not easy. Our aim was to study the association of common polymorphisms in genes of the NF-κB pathway in patients with psoriatic disease in order to dissect the contribution of this pathway in the appearance of each component (skin and joint) of the disease.

Patients and methods: We investigated the association between three common variants in NFKB1 (rs230526), NFKBIA (rs7152376), and NFKBIZ (rs3217713 indel) and the risk of developing psoriatic disease. We genotyped a total of 690 psoriatic disease patients and 550 controls. Patients with cutaneous psoriasis of at least 10 years of evolution without associated arthritis were defined to have pure cutaneous psoriasis (PCP).

Results: The rare NFKBIA rs7152376 C was significantly more frequent in the PsA group vs. controls (OR = 2.03 (1.3-3.1), p < 0.01). The difference was even higher between PsA and PCP patients (OR = 3.2 (2.1-5.1), p < 0.001). Neither NFKB1 rs230526 nor NFKBIZ rs3217713 indel was associated with the risk of developing psoriatic disease as a whole compared to controls.

Conclusions: Our study supports a significant effect of the NFKBIA gene on the risk of developing PsA, thus contributing to better discerning of the polymorphisms of this pathway that explain this risk within the spectrum of psoriatic disease. Additional studies with larger cohorts and from different populations are necessary to validate these results.

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adult
  • Arthritis, Psoriatic / genetics*
  • Arthritis, Psoriatic / metabolism*
  • Female
  • Genetic Association Studies
  • Genetic Predisposition to Disease / genetics*
  • Genotype
  • Humans
  • Logistic Models
  • Male
  • Middle Aged
  • NF-KappaB Inhibitor alpha / metabolism*
  • NF-kappa B / metabolism*
  • NF-kappa B p50 Subunit / genetics
  • Polymorphism, Single Nucleotide
  • Psoriasis / genetics
  • Risk Factors
  • Spain

Substances

  • Adaptor Proteins, Signal Transducing
  • NF-kappa B
  • NF-kappa B p50 Subunit
  • NFKB1 protein, human
  • NFKBIA protein, human
  • NFKBIZ protein, human
  • NF-KappaB Inhibitor alpha