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

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.

Clinical, laboratory, and genetic markers for the development or presence of psoriatic arthritis in psoriasis patients: a systematic review

“…Moderate evidence of a negative association was available for three markers: the presence of haplotype B*57-C*06 [ 97 , 99 ], the presence of HLA-C*06 [ 97 , 99 – 105 , 107 – 109 ], and the presence of the SNP rs2082412 in the IL12B gene [ 111 , 135 ].…”

Potential Differences in the Cardiometabolic Risk Profile of Patients with Psoriatic Disease according to Their HLA‐C∗06 Status

“…Furthermore, we do not know whether the genetic pathways to both cardiovascular comorbidity and psoriatic disease are common or different. However, a certain degree of commonality between psoriatic disease and some cardiovascular comorbidities as regards genes/proteins, biological processes, and inflammatory pathways has recently been highlighted [ 10 ]. Another study demonstrated shared genes between psoriasis and increased risk of dyslipidemia, hypertension, and cardiovascular disease [ 11 ].…”

Genetic Variants of the NF-κB Pathway: Unraveling the Genetic Architecture of Psoriatic Disease

“…The rare NFKBIA rs7152376 C was significantly more frequent in PsA vs. controls (OR 2.03). The difference was even higher between PsA vs. “pure” psoriasis (OR 3.2) [ 33 ]. These findings are in line with the results of a meta-analysis that described the association of rs12883343, in complete LD with rs7152376, and the risk of PsA [ 34 ].…”