Psoriatic arthritis: A systematic review of non‐HLA genetic studies and important signaling pathways

Abstract

Psoriatic arthritis (PsA) is a chronic inflammatory disease that primarily invades the musculoskeletal system and skin. 1 Usually, besides the arthritis damage, including arthritis, enthesitis, dactylitis and axial involvement, patients with PsA have psoriatic skin, such as epidermal hyperplasia, hyperkeratosis, parakeratosis, Munro's microabscesses and mixed dermal infiltrates. 2 In general, the severity of a patient's joint symptoms is consistent with the severity of the skin lesions. 3 In some cases, patients with PsA without psoriatic skin features only have arthritis damage or finger pain, which is similar to rheumatoid arthritis (RA). Generally, only about 13% of patients with PsA have rheumatoid factor in the blood and synovial fluid, while more than 80% of RA patients can be detected with rheumatoid factor. 4 The prevalence of PsA around the world is 0.3%-1%, 4 which differs in race and regions. In Western countries, the prevalence rates are about 0.02%, 0.42% and 0.25% in Sweden, Italy and the USA respectively, 5,6 whereas the rates are relatively lower in the Eastern countries, ranging from 0.01% to 0.1% in China, and <0.00001% in Japan. 6 PsA is not only harmful to an individual's health and life quality, but also may lead to a higher risk to suffer from cardiovascular events. 7 The pathogenesis of PsA is complex, and itmay be caused by genetic and environmental factors. Environmental aspects include infections (eg infectious diarrhea, human immunodeficiency virus infection), smoking, trauma and obesity. 8-11 In the researches for susceptibility genes for PsA, some human leukocyte antigen (HLA) genes are found as risk factors, and some HLA genes are found as protect factors. For instances, HLA-B*38 and HLA-Cw6 alleles are

Causal Association Between Inflammatory Bowel Disease and Psoriasis: A Two-Sample Bidirectional Mendelian Randomization Study

“…Evidence from meta-analyses and observational studies supports an underlying bidirectional relationship between psoriasis and inflammatory bowel disease (IBD), although mechanisms remain unclear (11,12). Many factors, such as common genetic susceptibility loci, clinical course, and immunologic features, are shared by psoriatic diseases and IBD (5,(13)(14)(15)(16), and IBD was considered a subsequent extra-articular manifestation of PsA which should be specially monitored in PsA patients according to the previous studies. However, basic and observational studies are susceptible to confounding factors, such as demographics or environmental exposure (17,18).…”

Biomarkers in psoriatic arthritis: A meta-analysis and systematic review

“…Specific non-HLA PsA variants have been identified in GWAS studies, including in the IL12B, NOS2 and IFIH1 regions as reported in a systematic review published in 2015 ( 141 ). Several signaling pathways possibly implicated in the pathogenesis of PsA were presented in a recent systematic review published in 2020 ( 142 ).…”

Advances of Genomic Medicine in Psoriatic Arthritis

“…As well as the association between HLA and PsA, there is evidence for the involvement of other non-HLA genes in the pathogenesis of the disease [23]. The first GWAS performed to identify genetic factors predisposing to PsA was carried out in 2008 [24].…”

“…In summary, the results from GWAS and successive meta-analyses have identified around 30 susceptibility non-HLA genes associated with PsA. We include a list of reported genome-wide PsA loci in Table 1 from the following studies [23][24][25][26][27][28]30,31,33]. Some of these genes have been described to be shared with other related diseases, such as AS, inflammatory bowel disease (IBD), RA or systemic lupus erythematosus (SLE) (Figure 1), being the most prominent genes: ERAP1, ERAP2, IL23A, IL23R, REL, RUNX3, STAT4, TLR4, TNIP1, TRAF3IP2, TYK2.…”