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, ). HLA-DRB 07 was associated with oligoarticular forms of PsA (OR 4.1, 95% CI: 1.8–9.3, ). The spondylitic forms overexpressed the antigen HLA-B 27 (OR 5.7, 95% CI: 2.4–13.6, ). MICA-A5.1 showed association with polyarthritis (OR 3.7, 95% CI: 1.5–8.8, ). 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. 1. Introduction 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]. Hence, the identification of the etiological factors would be an important advance because it may suggest therapeutic targets for the development of specific drugs and help establish the prognosis of patients. Linkage and association analyses have shown that the major histocompatibility complex (MHC) is the major genetic determinant related to psoriasis susceptibility. Within the MHC, HLA-C 06 is the allele that shows the strongest association with psoriasis [3, 4]. 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]. The association of HLA with PsA is more complex than that found in psoriasis. Although HLA-C 06, B 13, and B 57 have also been associated with PsA, the association is much weaker and seems to be related to psoriasis rather than arthritis [3, 4]. Centromeric to HLA-C, a susceptibility gene (MICA) has been associated with arthritis risk independently of C 06, though other authors have not confirmed this finding [5, 6]. Other nearby genes that are in linkage disequilibrium with HLA class I or
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