TNF-α Gene Polymorphisms: Association with Disease Susceptibility and Response to Anti-TNF-α Treatment in Psoriatic Arthritis

The tumor necrosis factor-a (TNF-alpha) gene has been proposed as a major candidate gene in psoriatic arthritis (PsA). TNF-alpha is a therapeutic target for patients responding poorly to conventional treatments. We investigated the role of single-nucleotide polymorphisms (SNPs) at positions -238, -308, and +489 of the TNF-alpha gene in the genetic susceptibility to PsA, in the severity of the disease, and, finally, in the response to TNF-alpha inhibitors (adalimumab, etanercept, or infliximab). Fifty-seven Caucasian PsA patients and 155 healthy matched controls were studied. The SNP +489 variant allele A was significantly associated with PsA susceptibility (P = 0.0136) and severity of clinical (Psoriasis Area and Severity Index score, American College of Rheumatology criteria, Disease Activity Score 28, and Disability Index Health Assessment Questionnaire) and laboratory (C-reactive protein and erythrocyte sedimentation rate) parameters (P-values ranging from 0.016 to 2.908 x 10(-12)). The difference in severity was accounted for by the differences between the AA and GA genotypes with respect to the GG genotype. The SNP +489A allele shows a trend of association with the response to PsA treatment with etanercept. These findings suggest a role of the SNP +489A allele in the susceptibility and severity of PsA.