Factors Associated with Radiographic Severity in Ankylosing Spondylitis with a Particular Focus on Investigating Interactions Between Environmental Factors and Genes: Results From a Multi-National Longitudinal Study
Objective: To investigate possible interaction of three genes (HLA-B27, RANK, and COX-1) and environmental factors on radiographic severity in Ankylosing Spondylitis (AS) patients. Methods: A total of 573 AS patients who fulfilled the modified New York Criteria and had at least two sets of radiographs were included in this longitudinal study. The radiographic severity was assessed using lateral cervical and lumbar radiographs as measured by modified Stoke Ankylosing Spondylitis Spine Score (mSASSS). A total of 1525 radiographs were used in the analysis. The interaction effect between each of the three genes (HLA-B27, RANK, and COX-1) and smoking or occupational physical activity level (OPAL) on radiographic severity in AS patients was investigated using a longitudinal mixed effects Zero-Inflated Negative Binomial (ZINB) regression model. Results: In a multivariable model, we observed a significant interaction between ever smoking status and HLA-B27 positivity on radiographic severity (Adjusted Relative Ratio (aRR): 1.29; 95% CI: 1.08, 1.55; p= 0.005). The model was adjusted for follow-up years, race, education, AS symptom duration, Nonsteroidal Anti-Inflammatory Drug (NSAID) Index, Tumor Necrosis Factors inhibitor (TNFi) use, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), C - reactive protein (CRP), interaction between comorbidity and gender, and interaction between comorbidity and fatigue. Similarly, the synergistic effect of OPAL and COX-1 allele on radiographic severity was found. Specifically, among patients with single copy of COX-1 allele, mSASSS was 2.15 times higher for patients who had high OPAL than those who had low OPAL (aRR: 2.15; 95% CI: 1.25, 3.71; p= 0.006). Furthermore, in a multivariable model, the significant interaction effect was observed between comorbidity and gender. Among male, those who had ?1 comorbidity had 1.50 times greater radiographic severity (or higher mSASSS) than those who did not have any comorbidity (aRR: 1.50; 95% CI: 1.32, 1.70; p= <.0001). The multivariable model was controlled for important covariates such as race, education, AS symptom duration, NSAID Index, TNFi use, BASFI, CRP, OPAL, and smoking*HLA interaction. Conclusions: A synergistic effect of smoking and HLA-B27 positivity on radiographic severity was observed. The finding suggest that there might be some possibilities of reducing the burden of disease through educating AS patients to quit cigarette smoking. Our results also suggest the possible OPAL and COX-1 interaction in relation to mSASSS. There might be some opportunities to educate AS patients to minimize the mechanical stress due to high OPAL, which may prevent them from having long-term disability. ^
Nepal, Bal Krishna, "Factors Associated with Radiographic Severity in Ankylosing Spondylitis with a Particular Focus on Investigating Interactions Between Environmental Factors and Genes: Results From a Multi-National Longitudinal Study" (2017). Texas Medical Center Dissertations (via ProQuest). AAI10617670.