Genetic Association Between TNF-Α (-308G>A) Polymorphism and Clinical Profile of Behçet’s Syndrome: Findings from An Italian Case-Control Analysis

Abstract

Background: Tumor necrosis factor-α (TNF-α) is a multifunctional proinflammatory cytokine involved in the pathogenesis of several immune-mediated disorders, including Behçet’s syndrome (BS) — a rare systemic vasculitis characterized by diverse clinical features. This study aimed to evaluate the potential association between the functional TNF-α promoter polymorphism (-308G>A, rs1800629) and both disease susceptibility and clinical expression of BS in an Italian population.

Methods: A total of 130 Italian patients diagnosed with BS and 100 age-, sex-, and ethnicity-matched healthy controls (HC) were enrolled from the Rheumatology Institute of Lucania, Italy. Demographic and clinical data were collected from medical records. Genomic DNA was extracted and genotyped using primer-specific PCR amplification followed by direct sequencing. Sequence analysis was performed using Mutation Surveyor (SoftGenetics, USA) and NCBI BLASTN tools for variant confirmation.

Results: A significantly higher frequency of the wild-type GG genotype was observed among BS patients compared to controls (81.5% vs 91%, p < 0.05), whereas the heterozygous GA genotype was more prevalent in patients (18.5%) than in controls (9%, p < 0.05). The GA genotype showed a significant association with disease susceptibility (OR = 2.29; 95% CI, 1.01–5.18). No significant correlations were found between the polymorphism and specific clinical features or overall disease severity as assessed by Krause’s index.

Conclusions: The TNF-α (-308G>A, rs1800629) GA genotype appears to confer an increased susceptibility to Behçet’s syndrome in the studied Italian cohort. However, no association was observed with clinical manifestations or disease severity. Larger, multicentric studies are warranted to validate these findings.