Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, United Kingdom.
Department of Rheumatology, The First Affiliated Hospital of Xiamen University, Medical College of Xiamen University, Xiamen, China.
Front Immunol. 2021 Feb 17;12:624632. doi: 10.3389/fimmu.2021.624632. eCollection 2021.
Genome-wide association studies (GWAS) have identified 113 single nucleotide polymorphisms (SNPs) affecting the risk of developing ankylosing spondylitis (AS), and an on-going GWAS study will likely identify 100+ new risk loci. The translation of genetic findings to novel disease biology and treatments has been difficult due to the following challenges: (1) difficulties in determining the causal genes regulated by disease-associated SNPs, (2) difficulties in determining the relevant cell-type(s) that causal genes exhibit their function(s), (3) difficulties in determining appropriate cellular contexts to interrogate the functional role of causal genes in disease biology. This review will discuss recent progress and unanswered questions with a focus on these challenges. Additionally, we will review the investigation of biology and the development of drugs related to the IL-23/IL-17 pathway, which has been partially driven by the AS genetics, and discuss what can be learned from these studies for the future functional and translational study of AS-associated genes.
全基因组关联研究（GWAS）已经确定了 113 个单核苷酸多态性（SNP）影响强直性脊柱炎（AS）的发病风险，而正在进行的 GWAS 研究可能会发现 100 多个新的风险位点。由于以下挑战，将遗传发现转化为新的疾病生物学和治疗方法一直具有难度：（1）确定受疾病相关 SNP 调控的因果基因的困难，（2）确定因果基因发挥功能的相关细胞类型（s）的困难，（3）确定适当的细胞环境以探究因果基因在疾病生物学中的功能作用的困难。本综述将讨论最近的进展和未解决的问题，重点关注这些挑战。此外，我们将回顾与 IL-23/IL-17 通路相关的生物学研究和药物开发，这些研究部分受到 AS 遗传学的推动，并讨论从这些研究中可以为 AS 相关基因的未来功能和转化研究学习到什么。
