Service of Clinical Pharmacology, Hospital Universitario de la Princesa, Instituto Teófilo Hernando, Universidad Autónoma de Madrid, Instituto de Investigación Sanitaria Princesa (IP), Madrid, Spain.
Pharmacogenomics J. 2013 Aug;13(4):297-305. doi: 10.1038/tpj.2012.53. Epub 2013 Jan 22.
Psoriasis (Ps) is a chronic inflammatory disease with an important genetic component. It shares pathophysiological mechanisms with other autoimmune diseases such as psoriatic arthritis (PsA), rheumatoid arthritis (RA) and Crohn's disease (CD). These conditions can be treated using biological drugs such as infliximab, adalimumab and etanercept, which selectively block the proinflammatory cytokine tumor necrosis factor (TNF)-α. Although these agents have greatly improved the prognosis of Ps, PsA, RA and CD, they do not cure the disease and are expensive; in addition, significant proportions of patients do not respond or develop serious adverse effects. Therefore, it is important to investigate biomarkers, such as gene polymorphisms, that can predict which patients will respond best to a specific drug. Some polymorphisms in genes TNF, TNF receptor superfamily 1B (TNFR1B) and TNFα-induced protein 3 gene (TNFAIP3) have been associated with response to anti-TNF therapy in patients with Ps. The present article reviews other polymorphisms that could also play a role in prediction of response to these treatments.
银屑病(Ps)是一种具有重要遗传成分的慢性炎症性疾病。它与其他自身免疫性疾病如银屑病关节炎(PsA)、类风湿关节炎(RA)和克罗恩病(CD)共享病理生理机制。这些疾病可以使用生物药物治疗,如英夫利昔单抗、阿达木单抗和依那西普,它们选择性地阻断促炎细胞因子肿瘤坏死因子(TNF)-α。尽管这些药物极大地改善了 Ps、PsA、RA 和 CD 的预后,但它们不能治愈疾病,而且价格昂贵;此外,相当一部分患者没有反应或出现严重的不良反应。因此,研究生物标志物(如基因多态性)以预测哪些患者对特定药物反应最好非常重要。一些 TNF、TNF 受体超家族 1B(TNFR1B)和 TNFα 诱导蛋白 3 基因(TNFAIP3)基因的多态性与 Ps 患者对抗 TNF 治疗的反应相关。本文综述了其他可能在预测这些治疗反应中发挥作用的多态性。