Toll-like receptor 2 gene variant associated with increased brucellosis risk: a case-control study

Brucellosis is a prevalent zoonotic disease in Iran, particularly in Hamadan province. Host genetic factors, especially single nucleotide polymorphisms (SNPs) in immune-related genes, may influence susceptibility to Brucella infection. This case-control study investigated associations between selected SNPs in Interferon-gamma (IFN-γ), Interleukin-4 (IL-4), Interleukin-8 (IL-8), Toll-like receptor 2 (TLR2), and Toll-like receptor 9 (TLR9) genes and brucellosis susceptibility in an Iranian population. A total of 120 patients with confirmed brucellosis and 120 age- and sex-matched healthy controls were enrolled from Hamadan province. Genotyping of IFN-γ (+ 874T/A, rs2430561), IL-4 (− 589 C/T, rs2243250), IL-8 (− 251 A/T, rs4073), TLR2 (rs3804099), and TLR9 (rs187084) was performed using PCR-restriction fragment length polymorphism (PCR-RFLP) and allele-specific PCR (AS-PCR). Demographic, clinical, and laboratory data were collected. Associations were evaluated using logistic regression models. The TLR2 rs3804099 polymorphism showed a significant association with brucellosis susceptibility. Under the codominant model, heterozygous TC (OR = 3.32, 95% CI: 1.72–6.41, p < 0.001) and homozygous TT (OR = 4.72, 95% CI: 1.80–12.39, p = 0.002) carriers had significantly increased risk compared to CC homozygotes. The dominant model (TC+TT vs. CC) also confirmed this association (OR = 3.50, 95% CI: 1.85–6.62, p < 0.001). Allele frequency analysis revealed that the T allele was significantly more frequent in cases than controls (50.83% vs. 36.67%, OR = 1.79, 95% CI: 1.24–2.58, p = 0.0014). No significant associations were observed for IFN‑γ, IL‑4, IL‑8, or TLR9 polymorphisms under any genetic model, although the recessive models for IFN‑γ (TT vs. AA+AT) and TLR9 (TT vs. CC+TC) showed protective trends that did not reach statistical significance (p = 0.053 and p = 0.064, respectively). However, given the limited statistical power of the study to detect moderate genetic effects for these secondary polymorphisms, these null findings should be interpreted with caution. Clinical symptoms included chills (85.8%), myalgia (81.5%), and back pain (81.0%), with elevated inflammatory markers and serological titers predominantly at 1:160 (p < 0.001 for all titers compared to controls). Our findings reveal a significant association between the TLR2 rs3804099 polymorphism and susceptibility to brucellosis, suggesting a potential role for TLR2 in host defense against Brucella . While this observation may contribute to future immunogenetic risk profiling, the preliminary and single‑center nature of our study precludes definitive clinical conclusions. Therefore, independent replication in larger, diverse populations and functional investigations are essential to validate these results and explore their translational potential.