-174G/C IL-6 gene promoter polymorphism predicts therapeutic response to TNF-α blockers

Abstract

Background: Although TNF-α blockade is a very effective therapy for psoriasis, not all patients achieve a favorable outcome. The association between IL-6 and psoriasis has been investigated but no papers have focused on the pharmacogenetics of IL-6.

Objective: To examine whether the G or the C allele, at position -174 in the promoter of IL-6, influences the relationships between body weight, body composition, and therapeutic response to TNF-α blockers in psoriasis.

Methods: Sixty patients with psoriasis were studied, at baseline and 6-month follow-up after therapy. Assessment of the -174G/C IL-6 polymorphism, Psoriasis Area and Severity Index and Disease Activity Score-28 scores, body weight (kg), BMI, body composition by Dual-energy X-ray absorptiometry, and systemic inflammation was performed.

Results: Relevant body composition changes occurred after therapy. Normal weight participants showed a greater increase in fat mass than lean mass, compared with obese participants. According to their genotypes, C(+) carriers showed a greater increase in lean mass and fat mass, at the abdominal region, with respect to C(-) carriers. C(+) carriers outweighed C(-) carriers in the group of treatment responders. A higher number of responders were present among normal weight participants, with respect to obese participants. Obesity and the -174G/C IL-6 polymorphism predicted poor response to TNF-α blockers [odds ratio for C(-) carriers, obese: 2.00 (confidence interval: 1.19-3.38; P≤0.05)].

Conclusion: Our data show that the G allele of the -174G/C IL-6 polymorphism and obesity can be considered as risk factors for the prognosis and management of psoriasis. This is the first study to suggest the -174G/C IL-6 polymorphism as a novel genetic marker of responsiveness to TNF-α blockers in psoriasis.