Genetic susceptibility factors for psoriatic arthritis

arc Epidemiology Unit, Manchester Academy of Health Sciences, The University of Manchester, Manchester, UK.
Current opinion in rheumatology (Impact Factor: 4.89). 03/2010; 22(2):152-6. DOI: 10.1097/BOR.0b013e32833669d2
Source: PubMed


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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    • "HLA class II antigens have also been associated with psoriasis and PsA. Thus, associations have been described between HLA-DRB * 07 and psoriasis and between DRB * 04 and PsA, although these associations have not been confirmed in all populations studied [3] [4] [7]. "
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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(1):570178. DOI:10.1155/2014/570178
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    • "Despite multiple susceptibility loci for psoriasis that have been identified, the PSORS1 locus located in the MHC class I region on chromosome 6p21.3 confers the most risk for psoriasis [1]. However, the extensive ranges of polymorphism and the preservation of HLA haplotypes in most populations have made it difficult to characterize the exact gene responsible for psoriasis susceptibility located in PSORS1. "
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    ABSTRACT: It has been shown that males with spondyloarthritis tend to suffer from more severe spinal disease while females are more likely to have peripheral joint involvement. Nevertheless, gender-related differences have not been thoroughly explored in psoriatic arthritis (PsA). In PsA, males accumulate more peripheral and axial joint damage compared to women. However, it is not clear whether these findings are secondary to differences in occupational physical activity, hormonal changes, or other factors. The present study analyzed the differences in clinical expression of PsA between men and women. We have also evaluated the possible existence of gender-linked differences in the distribution of genes and polymorphisms within the major histocompatibility complex and whether patients' age at the onset of psoriasis established any differences in these aspects. Women suffered more polyarthritis, greater functional impairment, and a larger number of swollen joints during followup. We appreciated a differential expression of certain MHC genes according to gender and age at onset of psoriasis. Our results point to the need to include patient's age at the onset of psoriasis and gender as key stratification elements in future studies of genetic associations in PsA.
    Clinical and Developmental Immunology 04/2013; 2013:482691. DOI:10.1155/2013/482691 · 2.93 Impact Factor
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    • "INTRODUCTION Psoriatic arthritis (PsA) is a chronic inflammatory musculoskeletal disease that occurs in the context of psoriasis vulgaris (PsV) affecting up to 30% of psoriasis patients (Gladman et al., 2005). Apart from the skin manifestation of PsV, the clinical phenotype of PsA overlaps with ankylosing spondylitis and rheumatoid arthritis (RA) (Castelino and Barton, 2010). Although PsV has a prevalence of up to 3% in populations of European ancestry (Bowcock and Barker, 2003; Griffiths and Barker, 2007), the estimated prevalence of PsA varies from 0.25 to 1% (Gladman et al., 2005). "
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    ABSTRACT: Psoriatic arthritis (PsA) is a chronic inflammatory musculoskeletal disease affecting up to 30% of psoriasis vulgaris (PsV) cases and approximately 0.25 to 1% of the general population. To identify common susceptibility loci, we performed a meta-analysis of three imputed genome-wide association studies (GWAS) on psoriasis, stratified for PsA. A total of 1,160,703 single-nucleotide polymorphisms (SNPs) were analyzed in the discovery set consisting of 535 PsA cases and 3,432 controls from Germany, the United States, and Canada. We followed up two SNPs in 1,931 PsA cases and 6,785 controls comprising six independent replication panels from Germany, Estonia, the United States, and Canada. In the combined analysis, a genome-wide significant association was detected at 2p16 near the REL locus encoding c-Rel (rs13017599, P=1.18 × 10(-8), odds ratio (OR)=1.27, 95% confidence interval (CI)=1.18-1.35). The rs13017599 polymorphism is known to associate with rheumatoid arthritis (RA), and another SNP near REL (rs702873) was recently implicated in PsV susceptibility. However, conditional analysis indicated that rs13017599, rather than rs702873, accounts for the PsA association at REL. 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.
    Journal of Investigative Dermatology 12/2011; 132(4):1133-40. DOI:10.1038/jid.2011.415 · 7.22 Impact Factor
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