Abstract / Summary
Background: Ankylosing spondylitis (AS) is a chronic inflammatory disease with musculoskeletal and extra-articular manifestations and associated cardiometabolic comorbidity. Brain-derived neurotrophic factor (BDNF) is involved in pain processing, neuroplasticity, inflammatory signaling, and metabolic regulation. The functional BDNF Val66Met polymorphism (rs6265) affects intracellular trafficking and activity-dependent BDNF secretion, but its clinical relevance in AS remains poorly characterized. This study evaluated the distribution of BDNF Val66Met and explored its associations with disease activity, inflammation, pain, depressive symptoms, and metabolic parameters in patients with AS. Methods: This single-center, cross-sectional study included 81 patients with AS and no healthy control group. Genotyping was performed using a tetra-primer amplification refractory mutation system polymerase chain reaction (T-ARMS-PCR) assay. Clinical assessment included the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Ankylosing Spondylitis Disease Activity Score based on C-reactive protein (ASDAS-CRP), pain Numerical Rating Scale (NRS), and depression subscale of the Hospital Anxiety and Depression Scale (HADS-D), together with CRP and metabolic measurements. ASDAS-CRP was designated as the primary clinical outcome. Statistical analyses included the Mann–Whitney U test, Fisher’s exact test, Spearman correlation with Benjamini–Hochberg false discovery rate correction, Hardy–Weinberg equilibrium testing, and exploratory multivariable linear and logistic regression. Results: The cohort comprised 81 patients (61 men and 20 women; mean age 53.2 ± 12.5 years). T-ARMS-PCR yielded 57 GG (70.4%) and 24 GA (29.6%) genotype calls, with no AA banding pattern observed; the Met allele frequency was 14.8%. The genotype calls were not independently confirmed by sequencing or restriction fragment length polymorphism analysis. No significant associations were identified between genotype and the clinical, inflammatory, or metabolic variables. Genotype was not associated with ASDAS-CRP after adjustment for age, sex, disease duration, current biologic-therapy status, and current smoking status (B = 0.045, 95% CI −0.238 to 0.328, p = 0.754; n = 80). After Benjamini–Hochberg correction, pain NRS remained correlated with BASDAI and CRP, while HADS-D remained correlated with BASDAI. Metabolic syndrome was present in 24 of 81 participants (29.6%) according to the harmonized Joint Interim Statement definition; medication use for individual metabolic components was not systematically available. Conclusions: No evidence of an association between BDNF Val66Met and disease activity, inflammatory markers, depressive symptoms, or metabolic parameters was found in this AS cohort. This study had 80% power to only detect an effect of Cohen’s d ≥ 0.69, and smaller genotype-associated differences cannot be excluded. The findings also describe the cardiometabolic profile of the cohort and the relationships among pain, inflammation, and depressive symptoms.