Exploratory study of DEFB1 genetic variants and human β-defensin-1 expression in monosodium urate crystal-induced arthritis: insights into innate immune regulation

Gout is an inflammatory arthritis triggered by the deposition of monosodium urate crystals and characterized by activation of innate immune pathways. Human β-defensin-1 (hBD-1), encoded by the DEFB1 gene, is an antimicrobial peptide with immunomodulatory functions. However, its role in gout-related inflammation remains unclear. This study aimed to investigate the relationship between DEFB1 variants (rs11362 and rs1800972) and circulating hBD-1 levels in gout.

A total of 81 individuals were enrolled, including 41 with gout and 40 healthy controls. Serum hBD-1 concentrations were quantified by ELISA, and genotyping was performed using TaqMan assays. Genetic associations were evaluated using logistic and linear regression models adjusted for relevant metabolic variables. An ANCOVA was performed to compare hBD-1 levels across genotypes, adjusting for age, serum urate, and triglyceride levels.

Serum hBD-1 levels were significantly lower in individuals with gout compared with controls (median 34.9 vs. 79.3 pg/mL, p < 0.0001). The rs11362 AA genotype was more frequent among controls and was associated with lower odds of gout across multiple inheritance models after adjustment (p < 0.05). In the overall cohort, this genotype was also associated with higher circulating hBD-1 concentrations (p < 0.0001). This association remained significant after adjusting for covariates in ANCOVA (p < 0.001). No significant associations were observed for the rs1800972 variant.

These results suggest that variation in the DEFB1 gene may be associated with differences in hBD-1 expression and gout status. The results provide preliminary evidence that supports a possible link between defensin-related innate immune regulation and gout-associated inflammation. However, given the exploratory design and limited sample size, these results should be interpreted as hypothesis-generating rather than confirmatory. Further studies in larger, well-characterized cohorts are needed to confirm these results and clarify their immunological relevance.