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.
Highlights
Psoriatic arthritis (PsA) is a complex disease in which environmental, host, and random factors interact resulting in disease in genetically susceptible individuals [1]
Associations have been described between HLA-DRB∗07 and psoriasis and between DRB∗04 and PsA, these associations have not been confirmed in all populations studied [3, 4, 7]
HLA-C∗06 was increased in both populations, whereas MICA-A9 was increased only in arthritic patients (Table 1)
Summary
Psoriatic arthritis (PsA) is a complex disease in which environmental, host, and random factors interact resulting in disease in genetically susceptible individuals [1]. This condition is associated with significant morbidity and mortality and is estimated to result in a cost to healthcare systems equivalent to that of rheumatoid arthritis [2]. Other HLA class I alleles associated with the disease (i.e., B13, B47, and B57) are due to linkage disequilibrium with HLA-C∗06 [3, 4]. Other nearby genes that are in linkage disequilibrium with HLA class I or MICA could determine susceptibility to PsA or further increase the risk of developing the disease. Associations have been described between HLA-DRB∗07 and psoriasis and between DRB∗04 and PsA, these associations have not been confirmed in all populations studied [3, 4, 7]
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