Faculty of Medicine, Memorial University of Newfoundland, 300 Prince Philip Drive, St John's, Newfoundland A1B 3V6, Canada.
Nat Rev Rheumatol. 2011 Nov 8;7(12):718-32. doi: 10.1038/nrrheum.2011.169.
Psoriatic arthritis (PsA), an inflammatory arthritis associated with psoriasis, has a wide spectrum of disease severity. The clinical heterogeneity in PsA probably reflects substantial genetic heterogeneity. In recent years, many genes that contribute to the pathogenesis of psoriasis and PsA have been identified, especially in Western cohorts. Emerging evidence from functional studies of candidate genes identified by genome-wide association studies is suggestive of an integrated, multi-tiered pathogenic model, comprising distinct signaling networks that affect skin barrier function, innate immune responses (involving NFκB and interferon signaling), and adaptive immune responses (involving CD8(+) T cells and type 17 T-helper-cell signaling). Although several genes--and variants thereof--within these pathways have been associated with susceptibility to psoriasis and PsA, replication in large multiethnic cohorts, fine mapping and resequencing efforts, together with functional studies of the variants, are warranted to better understand their role in disease susceptibility. With respect to pharmacogenetics, several candidate gene polymorphisms have been shown to influence responses to both traditional and biologic therapies in psoriasis and PsA, but confirmation in large prospective cohorts is required before the information can be used in the clinical setting.
银屑病关节炎（PsA）是一种与银屑病相关的炎症性关节炎，其疾病严重程度有广泛的范围。PsA 的临床异质性可能反映了实质性的遗传异质性。近年来，许多导致银屑病和 PsA 发病机制的基因已经被确定，特别是在西方队列中。全基因组关联研究鉴定的候选基因的功能研究的新证据表明存在一个综合的、多层次的致病模型，包括影响皮肤屏障功能、先天免疫反应（涉及 NFκB 和干扰素信号）和适应性免疫反应（涉及 CD8+T 细胞和 17 型 T 辅助细胞信号）的不同信号网络。虽然这些途径中的几个基因——及其变体——与银屑病和 PsA 的易感性有关，但在大型多民族队列中进行复制、精细定位和重测序工作，以及对变体的功能研究，对于更好地了解它们在疾病易感性中的作用是必要的。就药物遗传学而言，已经证明几个候选基因多态性会影响银屑病和 PsA 中传统和生物疗法的反应，但在临床环境中使用该信息之前，需要在大型前瞻性队列中进行确认。
