TNF polymorphisms are associated with the development of joint erosions in psoriatic arthritis
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KeywordsPsoriasis Psoriatic Arthritis Joint Erosion Periostitis Progressor Group
To determine whether functional cytokine gene polymorphisms influence disease susceptibility and phenotype in patients with psoriatic arthritis (PsA).
DNA was obtained from 147 PsA patients (mean age of arthritis onset = 35.2 ± 13.4 years; oligoarticular = 43 [29%], polyarticular = 104 [71%]) and 389 healthy Irish blood donors. Seven functional proinflammatory (IL-1β +3953, IL-6 -174, TNF-α -308, TNF-β +252) and anti-inflammatory (IL-10 -1082, IL-10 -592, IL-1Ra [intron 2, 86bp VNTR]) gene polymorphisms were detected by PCR and RFLP assays.
No significant difference in genotype frequencies was observed between the control population and the PsA population, and no association with ACR functional class, disease classification (polyarticular or oligoarticular), the presence of spinal involvement, or age of PsA onset was observed. Age of onset of psoriasis was significantly associated with the TNF-β (P = 0.0011) and TNF-α (P = 0.01) polymorphisms. The TNF-β B2/B2 and TNF-α -308 AA genotypes were associated with the earliest mean age of psoriasis onset. Plain radiographs of the hands and feet were obtained in 114 patients (64 with joint erosions, 48 with periostitis). The presence of joint erosions was significantly associated with the TNF-α -308 A (P < 0.0001) and TNFB1 (P = 0.0009) alleles. Sequential radiographs were obtained in 52/61 patients who presented with early PsA (<2 years' duration) with 19/52 (37%) increasing the number of joint erosions (progressors) over a median interval of 24 months. The TNF-α -308 A allele and the TNFB B1 allele were significantly increased in the progressor group (P = 0.014 and P = 0.048 respectively).
The TNF-α -308 and TNFB polymorphisms are significantly associated with the presence of joint erosions in PsA and with the progression of joint erosions in early PsA.