HLA-B27 may modulate the interaction between ERAP1 polymorphisms and smoking in ankylosing spondylitis patients

Abstract

Background 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. Methods and results 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. Conclusions The rs30187 and rs27044 variants of the ERAP1 gene appear to potentiate the effect of smoking in patients with AS carrying the B27 allele.

Literature review of non-pharmacological treatment for patients with axial spondyloarthritis

“…The exact mechanisms by which smoking influences the development and progression of axSpA are not fully understood; smoking may trigger and perpetuate inflammatory processes, contributing to disease progression and treatment non-responsiveness [8]. In addition, the complex interplay between smoking and genetic factors, such as variants of the endoplasmic reticulum aminopeptidase-1 gene may modulate the risk of axSpA [9]. Studies have demonstrated that smoking negatively affects bony progression based on the unit increase in the Ankylosing Spondylitis Disease Activity Score (ASDAS; odds ratio [OR] 2.15, 95% CI: 1.01 to 3.30) in axSpA patients [10].…”