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

Abstract

BackgroundPsoriasis (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.MethodsUsing 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.ResultsEleven 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.ConclusionAmong 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.

Polymorphisms in the NFkB, TNF‐alpha, IL‐1beta, and IL‐18 pathways are associated with response to anti‐TNF therapy in Danish patients with inflammatory bowel disease

“…Most of the SNPs assessed in our study have known biological effects thus allowing a biological interpretation of the observed associations based on increased or reduced gene activity as summarised in Table and illustrated in Figure . Among patients with CD, the association observed for the TNFRSF1A (rs4149570) polymorphism indicates that increased expression of the TNF‐α receptor 1, and thus increased activity of the TNF‐α pathway, was associated with beneficial response.…”

Genetically determined high activities of the TNF-alpha, IL23/IL17, and NFkB pathways were associated with increased risk of ankylosing spondylitis

“…Most of the SNPs assessed in our study have known biological effects thus allowing a biological interpretation of the observed associations based on increased or reduced gene activity as summarized in Table 2 [ 35 – 47 ]. The associations observed for the TNF (rs1800629 and rs361525) polymorphisms suggest that reduced TNF-α mRNA level and expression of TNF-α was associated with reduced risk of AS [ 48 , 49 ].…”

Analysis of association between cytokine gene polymorphisms and psoriatic disease in Russians of East Siberia

“…Similarly, there are conflicting results about association between another polymorphism of TNFA gene (rs361525) and PS or PsA (Loft et al, 2018). The curative effect of TNF-α blockers in patients with PS and PsA indicates that, to a certain degree, they share common immunopathogenesis (Mease, 2004).…”

“…Approximately one third of patients with PS develop psoriatic arthritis (PsA), a chronic inflammatory heterogeneous disease that can affect various distinct anatomical sites including peripheral and axial joints, entheses, skin and nails. Both PS and PsA are T-cell-mediated autoimmune diseases united under the term of psoriatic disease (Baliwag et al, 2015;Loft et al, 2018;Sakkas and Bogdanos, 2017). Their pathogenesis is largely driven by the dysregulation of pro-inflammatory and anti-inflammatory cytokines production.…”