Genetic susceptibility factors for psoriatic arthritis.
ABSTRACT Psoriatic arthritis (PsA) has a large genetic component to its heritability, yet investigation into the genetic basis of the disease has lagged behind other rheumatic diseases mainly because of the difficulty in defining classification criteria that would accurately differentiate it from other forms of inflammatory arthritis. However, using a variety of approaches, some confirmed associations have now been identified with PsA susceptibility, making a review of these recent developments timely.
Family studies continue to suggest a large genetic contribution to PsA. Using a candidate gene approach, genes robustly confirmed to be associated with psoriasis vulgaris (PsV) have also been found to be associated with PsA (HLA-Cw*0602, IL23R, IL12B). There is less overlap reported with rheumatoid arthritis (RA) than PsV susceptibility loci but one report suggests that the AFF3 locus may be associated with both RA and PsA.
Large, well powered genome-wide association studies are currently underway and should provide further insights into the cause of this common arthritic disease over the next few months. The bulk of evidence so far suggests that the genetic factors underlying PsV are also associated with PsA suggesting that future studies of PsV could include patients with PsA.
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ABSTRACT: With the aim of clarifying the role of several polymorphisms around the HLA-C locus in the clinical expression of PsA, the distribution of several polymorphic markers and genes located around the HLA-C locus was analyzed in a well-established cohort of 110 patients with PsA, 50 patients with psoriasis alone, and 110 healthy controls. The frequency of these genes was also analyzed by PsA articular models, based on three main subgroups: oligoarthritis, polyarthritis, and spondylitis. Distal interphalangeal joint (DIP) involvement was associated with the presence of MICB-CA20 (OR 6.0, 95% CI: 1.58-22.69, P = 0.005). HLA-DRB∗07 was associated with oligoarticular forms of PsA (OR 4.1, 95% CI: 1.8-9.3, P = 0.0007). The spondylitic forms overexpressed the antigen HLA-B∗27 (OR 5.7, 95% CI: 2.4-13.6, P = 0.0001). MICA-A5.1 showed association with polyarthritis (OR 3.7, 95% CI: 1.5-8.8, P = 0.006). Genes telomeric to HLA-C were overexpressed in psoriasis but not in PsA subphenotypes. This study shows that the region centromeric to HLA-C is a key region that expresses not only disease risk genes but also genes that help explain the phenotypic variability of PsA.01/2014; 2014:570178. DOI:10.1155/2014/570178
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ABSTRACT: Psoriatic arthritis is a major comorbidity of psoriasis that significantly impairs quality of life and physical function. Because skin lesions classically precede joint symptoms, dermatologists are in a unique position to identify patients at risk for psoriatic arthritis before irreversible joint damage occurs. Here we review the literature to identify the clinical and genetic factors most highly associated with development of psoriatic arthritis, with the goal of assisting dermatologists in risk-stratifying their psoriasis patients.