Division of Rheumatology, Toronto Western Hospital, 399 Bathurst Street, Toronto, ON M5T 2S8, Canada.
Curr Rheumatol Rep. 2012 Oct;14(5):383-9. doi: 10.1007/s11926-012-0268-0.
Endoplasmic reticulum aminopeptidase 1 (ERAP1) and interleukin-23 receptor (IL-23R) gene polymorphisms were found to be associated with ankylosing spondylitis (AS) in a nonsynonymous single nucleotide polymorphism association study, and this has been replicated in several studies across different populations. ERAP1 variants could lead to significant changes in the repertoire of peptides presented by MHC-I. Reading this in conjunction with the known association of AS with HLA-B27, a functional interaction between ERAP1 and HLA-B27 is very likely. ERAP1 has additionally been shown to be involved in cytokine receptor shedding. The IL-23R is one of the two receptors that mediate the action of IL-23. AS is associated with the same polymorphisms of IL-23R as those linked to psoriasis and inflammatory bowel disease. This suggests common genetic risks linking AS and extra-articular manifestations. This review focuses on the pathogenic potential of these two genes in AS.
内质网氨肽酶 1（ERAP1）和白细胞介素-23 受体（IL-23R）基因多态性与强直性脊柱炎（AS）相关，这在非同义单核苷酸多态性关联研究中得到了证实，并且在不同人群的多项研究中得到了复制。ERAP1 变体可能导致 MHC-I 呈递的肽库发生显著变化。结合已知的 AS 与 HLA-B27 的关联，ERAP1 与 HLA-B27 之间很可能存在功能相互作用。此外，ERAP1 已被证明参与细胞因子受体脱落。IL-23R 是介导 IL-23 作用的两个受体之一。AS 与银屑病和炎症性肠病相关的 IL-23R 相同的多态性相关。这表明 AS 和关节外表现之间存在共同的遗传风险。本文重点介绍了这两个基因在 AS 中的致病潜力。
