Psoriatic arthritis (PsA) is a chronic inflammatory arthritis associated with psoriasis and, despite the larger estimated heritability for PsA, the majority of genetic susceptibility loci identified to date are shared with psoriasis. Here, we present results from a case–control association study on 1,962 PsA patients and 8,923 controls using the Immunochip genotyping array. We identify eight loci passing genome-wide significance, secondary independent effects at three loci and a distinct PsA-specific variant at the IL23R locus. We report two novel loci and evidence of a novel PsA-specific association at chromosome 5q31. Imputation of classical HLA alleles, amino acids and SNPs across the MHC region highlights three independent associations to class I genes. Finally, we find an enrichment of associated variants to markers of open chromatin in CD8+ memory primary T cells. This study identifies key insights into the genetics of PsA that could begin to explain fundamental differences between psoriasis and PsA.
Objective. Psoriatic arthritis (PsA) is a common inflammatory joint disease distinct from other chronic arthritides and frequently accompanied by psoriasis vulgaris. In a first genome-wide association study (GWAS), we were able to identify several genetic risk factors. However, even combined with previously identified factors, the genetic contribution to disease was not fully explained. Therefore, we undertook this study to investigate further 17 loci from our GWAS that did not reach genome-wide significance levels of association in the initial analysis.Methods. Twenty-one of 22 single-nucleotide polymorphisms were successfully genotyped in independent cohorts of 1,398 PsA patients and 6,389 controls and in a group of 964 German patients with psoriasis vulgaris.Results. Association with a RUNX3 variant, rs4649038, was replicated in independent patients and controls and resulted in a combined P value of 1.40 ؋
The aim of this study was to identify potential markers of aggressive joint manifestations and HLA associations in patients with psoriatic arthritis (PsA) in northern Sweden. Patients with PsA were examined clinically, with laboratory tests and radiologically. The classification of the disease was based on peripheral and/or axial engagement. HLA B17, B37 and B62 were significantly increased in PsA patients. Univariate analyses suggest that the HLA antigens B37, B62 and some clinical variables were associated with disease course. However, in multivariate analyses distal interphalangeal joint affliction and polyarticular manifestations were the only variables remaining significantly associated with irreversible joint destruction or deformity. There were no significant effects of HLA antigens. In this cross-sectional study, clinical manifestations were more reliable predictors of aggressive joint damage than were specific HLA antigens. However, HLA antigens seemed to modify the expression of the joint disease rather than being involved in joint disease susceptibility.
Psoriatic arthritis (PsA), an inflammatory joint disease associated with psoriasis of the skin, has a heterogeneous pattern expressed by different manifestations, such as mild mono-oligoarthritis, a very severe, erosive and destructive polyarthritis indistinguishable from rheumatoid arthritis, and spondylarthropathy with axial involvement or enthesitis. The disease pattern often differs between patients as well as within the same patient over time. Measurable inflammatory activity is not always evident. Early detection of inflamed joints or axial involvement in patients with PsA is important in order to reduce the inflammation and prevent destruction, deformity and functional disability in the joints involved. Several factors, e.g., genetic, immunological, environmental and vascular, have been proposed to be of importance for the aetiology, the expression and prognosis of PsA. The basic treatment for PsA has been administration of non-steroid anti-inflammatory drugs (NSAIDs). Few disease modifying anti-rheumatic drugs (DMARDs) have been available due to a lack of efficacy of most of the DMARDs used for other rheumatic diseases. New insights into genetic, immunological and vascular factors in PsA are of interest as possible targets for future therapy and will be discussed in this review.
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