Genetic variants in the genes Tnip1 and TNFAIP3 are both strongly associated with susceptibility to autoimmune chronic inflammatory diseases such as psoriasis vulgaris and systemic lupus erythematosus (SLE) in humans.
We identified significant associations of the single nucleotide polymorphisms with PsV risk at TNFAIP3-interacting protein 1and the major histocompatibility complex region (P = 3.7 × 10<sup>-10</sup> and 6.6 × 10<sup>-15</sup>, respectively).
These results suggest that the expression level of TNFAIP3 plays an important role in the pathology of psoriasis vulgaris and that the loss of upregulation of TNFAIP3 expression may contribute to the severity of psoriasis vulgaris.
We found that risk heterogeneity between PsA and PsC might be driven by HLA-B amino acid position 45 (Pomnibus = 2.2 × 10(-11)), indicating that different genetic factors underlie the overall risk of PsV and the risk of specific PsV subphenotypes.
For psoriasis vulgaris, nine alleles were strongly associated with susceptibility in white subjects and five in Asians, with HLA-Bw*37 and HLA-B*57 in both; three alleles were strongly protective in white subjects and one in Asians, with none in common.
Parametric linkage analysis accounting for marker-trait disequilibrium in psoriasis vulgaris pedigrees yielded most significant results for a locus close to HLA-B and -C. Furthermore, we found that susceptibility is linked to at least three different ancestral HLA haplotypes; among them, HLA-Cw7-B8-DRB1*0301-DQB1*02 is linked to PsV for the first time.
Genetic variants in the genes Tnip1 and TNFAIP3 are both strongly associated with susceptibility to autoimmune chronic inflammatory diseases such as psoriasis vulgaris and systemic lupus erythematosus (SLE) in humans.
Meanwhile, its CC genotype and C allele were positively associated with the early onset of PsV (P = .036, OR = 2.080, 95% CI = 1.044-4.145; P = .034, OR = 1.443, 95% CI = 1.028-2.024) and increased PsV risk in the subgroup with family history (P = .029, OR = 2.149, 95% CI = 1.075-4.296; P = .027, OR = 1.466, 95% CI = 1.044-2.059).ERAP1 gene rs26653 polymorphism may increase the risk of PsV in Chinese Han population.
The association of ERAP1 and ERAP2 single nucleotide polymorphisms and their haplotypes with psoriasis vulgaris is dependent on the presence or absence of the HLA-C*06:02 allele and age at disease onset.
In PsV a significant association was found for IL28RA (rs4649203, P = 9.53 × 10(-7)), TNIP1 (rs17728338, P = 1.21 × 10(-4)) and ERAP1 (rs27524, P = 1.17 × 10(-3)).
In PsV a significant association was found for IL28RA (rs4649203, P = 9.53 × 10(-7)), TNIP1 (rs17728338, P = 1.21 × 10(-4)) and ERAP1 (rs27524, P = 1.17 × 10(-3)).
We hypothesize that c-Rel, as a member of the Rel/NF-κB family, is associated with PsA in the context of disease pathways that involve other identified PsA and PsV susceptibility genes including TNIP1, TNFAIP3, and NFκBIA.
In recent genome-wide association studies for psoriatic arthritis (PsA) and psoriasis vulgaris, common coding variants in the TRAF3IP2 gene were identified to contribute to susceptibility to both disease entities.
A stratified analysis of our datasets including only PsA cases (1,922 cases compared to 8,037 controls, P = 4.57 × 10⁻¹² for rs33980500) suggested that TRAF3IP2 represents a shared susceptibility for PsV and PsA.
Functional assays showed reduced binding of this TRAF3IP2 variant to TRAF6, suggesting altered modulation of immunoregulatory signals through altered TRAF interactions as a new and shared pathway for PsA and PsV.