TLR4 and TNF-α single nucleotide polymorphisms in patients with brucellosis: Association with infection complications.

Abstract

Objectives: To investigate associations of the carriage of single nucleotide polymorphisms (SNPs) of proteins involved in the immune response of patients with brucellosis.

Methods: A case control study of patients with brucellosis upon WHO criteria. Blood genomic analysis was performed by RFLP- PCR for the detection of SNPs: i) at promoters -376 G > A (rs1800750); -308 G > A (rs 1,800,629); -238 G > A (rs361525) of the TNF gene, ii) at -896 A > G Asp299Gly (rs4986790) and -1196 C > T Thr399Ile (rs4986791) positions of the TLR-4 gene. Logistic regression analysis of factors related to brucellar spondylodiscitis was performed.

Results: Patients with brucellosis (n = 105) were male (n = 67, 63.8 %); mean age (SD): 49.51(18.31); spondylodiscitis (n = 30), sacral osteomyelitis (n = 21). Carriage of the minor frequency A alleles at -238 of the promoter region of TNF was greater in patients than in controls (11.4% vs 2.6 %, p < 0.001). In a stepwise regression model including host variables and TNF-238 G A^-1 genotype, only the last one was associated with brucellar spondylodiscitis [OR 2.91 (CI95 % 1.02-8.31), p = 0.047].

Conclusions: In our cohort, the association of one TNF SNP of patients with brucellosis, in particular spondylodiscitis, might be prognostic whereas further investigation of the exact role in the host immune response is required.