Toll-like receptor 9 (TLR9) genetic variants rs187084 and rs352140 confer protection from Behcet's disease among Iranians.

Background: Behcet's disease (BD) is a multisystem and multifactorial autoimmune disease characterized by relapsing episodes of oral aphthae, genital ulcers, and ocular and skin lesions. Toll-like receptor 9 (TLR9) has pro-inflammatory roles and its genetic variants might be involved in the pathogenesis of inflammatory diseases.  METHODS: Two hundred five BD patients and 207 age and sex-matched healthy controls were evaluated for TLR9 single nucleotide polymorphisms - 1486 T/C (rs187084) and + 2848:G/A (rs352140) using polymerase chain reaction-restriction fragment length polymorphism (RFLP-PCR).

Results: Healthy individuals had a significantly higher frequency of rs187084 AG and AG + GG genotypes than BD patients (p = 0.02 and p = 0.018; respectively). Of interest, healthy males had a significantly higher frequency of rs187084 AG + GG genotype and G allele than male BD patients (p = 0.035 and p = 0.045; respectively). However, rs187084 AG genotype and G allele frequencies were significantly higher in male patients with genital aphthous (p = 0.01 and p = 0.046; respectively). Furthermore, a significantly higher frequency of rs352140 CT and TT + CT genotypes was detected in healthy individuals than in BD patients (p = 0.01, and p = 0.032; respectively). Such results were also seen in healthy females than female patients (p = 0.001, and p = 0.004; respectively). Haplotype analysis revealed a significantly higher frequency of A-C and G-C haplotypes among patients and healthy subjects, respectively (p = 0.002 and p = 0.000; respectively).

Conclusion: Our data suggested that rs187084 AG and AG + GG genotypes and rs352140 CT and TT + CT genotypes protect Iranian individuals from BD but rs187084 AG genotype and G allele predispose male BD individuals to genital aphthous. However, additional studies are required to verify these results.