Rs582757

rs582757 variant is located within an intron of TNFAIP3 gene that encodes for tumor necrosis factor alpha-inducible protein 3 that has been identified as a candidate causal variants of psoriasis.

TNFAIP3 gene encodes an ubiquitin-modifying protein, A20, which is a critical regulator of cytokine-mediated immune and inflammatory responses. In previous work TNFAIP3 polymorphisms were found to be associated with multiple autoimmune diseases such as psoriasis, systemic lupus erythematosus, rheumatoid arthritis, systemic sclerosis and celiac disease.

Psoriasis is a common and chronic autoimmune disease characterized by skin lesions, which are raised, often red and scaly. These skin lesions vary in severity from small-localized patches to complete body coverage. Five different types of psoriasis have been categorized, plaque (most common), guttate, inverse, pustular and erythrodermic. Currently the cause of psoriasis is not fully known, although it is generally considered to hold a strong genetic risk component, environmental factors are thought to elicit onset of disease.

To evaluate the genetic component, {{PMID| 25521225} highlights TNFAIP3 for fine-scale association signal in psoriasis to identify candidate causal variants. Imputation and meta-analysis was performed within the TNFAIP3 region in five different European ancestry cohorts (4,704 cases and 7,805 controls). Identification of 49 variants whose significance exceeded a corrected Bonferroni threshold resulted, with the top variant being rs582757 with the risk allele "C" (P-value = 6.07 x 10-12, odds ratio (OR) = 1.24). Function annotation on rs582757 identified strong evidence of regulatory potential, especially within long noncoding RNAs that contributes to transcription factor binding to NFKB1, IRF4 and SMARCA4.