TNFAIP3 haplotypes modulate susceptibility to Behçet’s disease: evidence from an Iranian case-control study

Behçet’s disease (BD) is a chronic inflammatory disorder characterized by recurrent mucocutaneous, ocular, articular, and systemic inflammation. TNFAIP3 encodes A20, a negative regulator of NF-κB signaling, and its variants are implicated in immune-mediated diseases. This case-control study investigated whether TNFAIP3 SNPs rs610604 and rs7753873 are associated with BD susceptibility and clinical features in an Iranian population. 232 BD patients and 281 healthy controls were included; genotyping was performed using PCR-RFLP. The rs610604 GG genotype and G allele were suggestively protective against BD (OR = 0.51, 95% CI: 0.26–1.00, p = 0.048; OR = 0.75, 95% CI: 0.56–0.99, p = 0.044), although these associations did not remain significant after correction for multiple testing. The GG genotype was nominally associated with reduced genital ulcers (OR = 0.31, p = 0.04) and joint involvement (OR = 0.31, p = 0.04). GT genotype (OR = 0.40, p = 0.004) and G allele (OR = 0.50, p = 0.0026) protected against joint involvement. rs7753873 showed no independent associations. Haplotype analysis showed G–C and T–A increased BD risk (OR = 5.50, p < 0.001; OR = 1.28, p = 0.045), whereas G–A and T–C were protective (OR = 0.38, p < 0.001; OR = 0.56, p = 0.029); only G-C and G-A survived correction. Exploratory findings suggest TNFAIP3 haplotypes may influence disease susceptibility more robustly than individual SNPs.