Laboratorio de Líquido Sinovial, Instituto Nacional de Rehabilitación "Luis Guillermo Ibarra Ibarra", Mexico City, Mexico.
Biology Department, Facultad de Química, Universidad Nacional Autónoma de Mexico (UNAM), Mexico City, Mexico.
Mol Biol Rep. 2022 Jul;49(7):6423-6431. doi: 10.1007/s11033-022-07456-4. Epub 2022 Apr 16.
Ankylosing spondylitis (AS) is an autoimmune disease that affects the enthesis and synovial membrane of the spine, the sacroiliac vertebrae and peripheral joints. Genetic susceptibility to AS is mainly due to the presence of the HLA-B*27 (B27) allele, and endoplasmic reticulum aminopeptidase-1 (ERAP-1) plays a key role in antigen processing and presentation to HLA class I molecules. Tobacco consumption is one of the main environmental factors involved in the pathogenesis of various diseases, including AS. The objective of the present study was to evaluate the association and the interactive effects of variants of the ERAP1 gene with smoking in modulating the risk of AS.
A case-control study in the Mexican population. The association of two functional variants of the ERAP1 gene (rs30187 and rs27044) in patients with AS was analyzed by the allelic discrimination method using TaqMan probes. B27 was typified by PCR-SSP. The interaction between the variants of ERAP1 and B27 and smoking was assessed using the multifactorial dimensionality reduction (MDR) method. There was no significant association of the two variants of ERAP1 in the cases compared with the controls (P > 0.05); however, a strong interaction between the variants and smoking could be demonstrated, with entropy values of 4.97% for rs30187 and 5.13% for rs27044. In addition, these interaction effects were increased in patients carrying the B27 allele.
The rs30187 and rs27044 variants of the ERAP1 gene appear to potentiate the effect of smoking in patients with AS carrying the B27 allele.
强直性脊柱炎（AS）是一种自身免疫性疾病，影响脊柱的附着点和滑膜、骶髂关节和外周关节。AS 的遗传易感性主要归因于 HLA-B*27（B27）等位基因的存在，内质网氨肽酶-1（ERAP-1）在抗原加工和呈递给 HLA Ⅰ类分子中发挥关键作用。吸烟是包括 AS 在内的多种疾病发病机制中的主要环境因素之一。本研究旨在评估 ERAP1 基因变体与吸烟之间的关联及其相互作用，以调节 AS 的发病风险。
在墨西哥人群中进行了病例对照研究。采用 TaqMan 探针的等位基因鉴别方法分析了 ERAP1 基因的两个功能变体（rs30187 和 rs27044）在 AS 患者中的关联。通过 PCR-SSP 对 B27 进行分型。使用多因子维度降低（MDR）方法评估 ERAP1 变体与 B27 和吸烟之间的相互作用。与对照组相比，病例组中两个 ERAP1 变体没有显著关联（P>0.05）；然而，可以证明变体与吸烟之间存在强烈的相互作用，rs30187 的熵值为 4.97%，rs27044 的熵值为 5.13%。此外，这些相互作用效应在携带 B27 等位基因的患者中增加。
ERAP1 基因的 rs30187 和 rs27044 变体似乎增强了携带 B27 等位基因的 AS 患者吸烟的效应。
