-174G/C IL-6 gene promoter polymorphism predicts therapeutic response to TNF-α blockers
-174G/C IL-6 gene promoter polymorphism predicts therapeutic response to TNF-α blockers
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DOI：
10.1097/fpc.0b013e32834e5e7b
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发表时间：
2012-02-01
影响因子：
2.6
通讯作者：
De Lorenzo, Antonino
中科院分区：
文献类型：
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作者：
Di Renzo, Laura;Bianchi, Alessia;De Lorenzo, Antonino
背景虽然 TNF-α 阻断是治疗银屑病的一种非常有效的疗法，但并非所有患者都能获得良好的结果。 IL-6 与银屑病之间的关联已被研究，但没有论文关注 IL-6 的药物遗传学。 目的 检测 IL-6 启动子第 174 位的 G 或 C 等位基因是否影响银屑病中体重、身体成分和 TNF-α 阻滞剂治疗反应之间的关系。 方法 对 60 名银屑病患者进行了基线研究 以及治疗后6个月的随访。评估 - 174G/C IL-6 多态性、银屑病面积和严重程度指数以及疾病活动性 Score-28 评分、体重（kg）、BMI、双能 X 射线吸收测定法的身体成分以及全身炎症。 结果 治疗后出现相关身体成分变化。与肥胖参与者相比，正常体重参与者的脂肪量增加幅度大于去脂量。根据其基因型，与 C(-) 携带者相比，C(+) 携带者腹部的瘦体重和脂肪量增加幅度更大。在治疗反应者组中，C(+) 携带者的体重超过 C(-) 携带者。与肥胖参与者相比，正常体重参与者中有更多的响应者。肥胖和 - 174G/C IL-6 多态性预测对 TNF-α 阻滞剂的反应较差[C(-) 携带者，肥胖的比值比：2.00（置信区间：1.19-3.38；P
Background Although TNF-alpha 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-alpha 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-alpha blockers [odds ratio for C(-) carriers, obese: 2.00 (confidence interval: 1.19-3.38; P