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.
Highlights
In recent years, great advances have been made in the knowledge on the genetic basis of psoriasis and psoriatic arthritis (PsA). e nuclear factor-kappa beta (NF-κB) is pivotal in the regulation of several biological processes, and its deregulation would affect immunological pathways that have been implicated in several pathological processes [1,2,3].e NF-κB pathway would play an important role in psoriasis [4,5,6,7,8]
Individuals affected with psoriasis for 10 or more years without developing arthritis were classified as pure cutaneous psoriasis (PCP; n 309) cases. e 10-year period is the average time between the onset of psoriasis and the onset of arthritis. us, patients with psoriasis duration of this magnitude will most likely not develop arthritis [23]. erefore, the population of PCP is a good comparator in relation to those patients with PsA
We investigated the association between three common variants in NFKB1, NFKBIA, and NFKBIZ and the risk of developing psoriasis/PsA or their main clinical outcomes
Summary
Great advances have been made in the knowledge on the genetic basis of psoriasis and psoriatic arthritis (PsA). e nuclear factor-kappa beta (NF-κB) is pivotal in the regulation of several biological processes, and its deregulation would affect immunological pathways that have been implicated in several pathological processes [1,2,3].e NF-κB pathway would play an important role in psoriasis [4,5,6,7,8]. Atypical nuclear proteins bind to NF-κB and regulate its BioMed Research International function Among these nuclear inhibitors, IκBζ (encoded by NFKBIZ) would play a prominent role in the pathogenesis of psoriasis [7, 10]. 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. Our study supports a significant effect of the NFKBIA gene on the risk of developing PsA, 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
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