Centre for Genetics and Genomics Versus Arthritis, Centre for Musculoskeletal Research, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, The University of Manchester, Manchester, United Kingdom.
Centre for Genetics and Genomics Versus Arthritis, Centre for Musculoskeletal Research, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, The University of Manchester, Manchester, United Kingdom; NIHR Manchester Biomedical Research Centre, Central Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, United Kingdom.
Clin Ther. 2023 Sep;45(9):810-815. doi: 10.1016/j.clinthera.2023.07.003. Epub 2023 Jul 27.
Approximately 30% of patients with psoriasis will develop psoriatic arthritis (PsA), leading to a decreased quality of life for the patient caused by increasing disability and additional health complications. The identification of risk factors for the development of PsA would facilitate the development of risk prediction models in which patients with psoriasis at high risk of developing PsA could be targeted in a stratified medicine approach, enabling early intervention and treatment. PsA is known to have a genetic contribution to susceptibility, and the identification of genetic risk factors that differentiate PsA from cutaneous-only psoriasis is a key area of research. This narrative review summarizes the discovery of genetic risk factors and, with the aid of a primer on risk prediction models, discusses their potential role for the classification of PsA risk and diagnosis.
All relevant research articles were identified through searches of the PubMed database for literature published up until December 2022. Search terms included psoriatic arthritis, genetic susceptibility, genetic association, genome-wide association study, GWAS, prediction, and polygenic risk score.
The current literature reveals considerable overlap between the genetic susceptibility loci for PsA and psoriasis. Several PsA-specific genetic risk factors have been reported, and most notably these implicate the HLA-B and IL23R genes. Efforts to include genetic risk factors in prediction models for the development of PsA have reported good discrimination.
Key messages emerging from this narrative are as follows: the limited number of PsA-specific susceptibility loci reported to date suggest larger studies are required, facilitated by international collaboration, to achieve the power to detect further genetic factors; the early promising results for genetic-based risk prediction require further validation in independent datasets; and risk prediction models combining clinical and genetic risk factors have yet to be explored.
约 30%的银屑病患者会发展为银屑病关节炎（PsA），这会导致患者的生活质量下降，因为残疾程度增加和出现更多健康并发症。确定发生 PsA 的风险因素将有助于开发风险预测模型，通过分层医学方法，可以针对患有银屑病且发生 PsA 风险高的患者，实现早期干预和治疗。已知 PsA 的易感性与遗传因素有关，确定将 PsA 与单纯皮肤银屑病区分开来的遗传风险因素是一个关键的研究领域。本综述总结了遗传风险因素的发现，并借助风险预测模型入门知识，讨论了它们在 PsA 风险分类和诊断中的潜在作用。
通过检索 PubMed 数据库，查找截至 2022 年 12 月发表的所有相关研究文章，确定所有相关研究文章。检索词包括银屑病关节炎、遗传易感性、遗传关联、全基因组关联研究、GWAS、预测和多基因风险评分。
目前的文献表明，PsA 和银屑病的遗传易感性位点之间存在很大的重叠。已经报道了几个特定于 PsA 的遗传风险因素，其中最值得注意的是 HLA-B 和 IL23R 基因。将遗传风险因素纳入 PsA 发展预测模型的努力报告了良好的区分度。
本综述得出的主要结论如下：迄今为止报道的 PsA 特异性易感性基因座数量有限，这表明需要通过国际合作进行更大规模的研究，以获得检测更多遗传因素的能力；基于遗传的风险预测的早期有希望的结果需要在独立数据集进一步验证；结合临床和遗传风险因素的风险预测模型尚未得到探索。
