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. 2025 Jan:131:121-124.
doi: 10.1016/j.ejim.2024.10.006. Epub 2024 Oct 16.

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

Efthymia Giannitsioti  1 , Angelos Stefos  2 , Georgia Damoraki  3 , Sarah Georgiadou  2 , Maria Pavlaki  4 , Evangelos J Giamarellos-Bourboulis  3 , George Dalekos  2
Affiliations

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

Efthymia Giannitsioti et al. Eur J Intern Med. 2025 Jan.

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.

Keywords: Brucellosis; Single nucleotide polymorphism; Spondylodiscitis; TLR4; TNF-a; Vertebral osteomyelitis.

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Conflict of interest statement

Declaration of competing interest E. J. Giamarellos-Bourboulis has received honoraria from Abbott Products Operations, bioMérieux, France, Brahms GmbH, GSK, Sobi AB and Xbiotech Inc; independent educational grants from Abbott Products Operations, bioMérieux Inc, Johnson & Johnson, MSD, UCB, Swedish Orphan Biovitrum AB; and funding from the Horizon 2020 European Grants ImmunoSep and RISCinCOVID and the Horizon Health grants EPICCROWN-2, POINT and Homi-Lung (granted to the Hellenic Institute for the Study of Sepsis). G. Dalekos is an advisor or lecturer for Pfizer, Roche, Sanofi and Sobi, and received research grants from Gilead and has served as PI in studies for Gilead, Novo Nordisk, Genkyotex, Regulus Therapeutics Inc, Tiziana Life Sciences, Bayer, Astellas, Pfizer, Amyndas Pharmaceuticals, CymaBay Therapeutics Inc., Sobi and Intercept Pharmaceuticals.

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