Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 18, Issue 7, Pages -Publisher
MDPI
DOI: 10.3390/ijms18071432
Keywords
disease association; gene polymorphism; nuclear factor-kappa B pathway; rheumatoid arthritis; Toll-like receptors
Funding
- National Science Center [UMO-2016/21/B/NZ5/01901]
- Wroclaw Centre of Biotechnology program-The Leading National Research Centre (KNOW) [519-1-4-3-174]
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Genes involved in regulation of the nuclear factor-kappa B (NF-kappa B)-pathway are suggested to play a role in pathogenesis of rheumatoid arthritis (RA). In the present study, genetic polymorphisms of TLR2, TLR4, TLR9 and NF-kappa B1 genes were investigated to assess their associations with RA susceptibility, progression and response to anti-TNF-alpha therapy. A group of 110 RA patients and 126 healthy individuals were genotyped for TLR2 (rs111200466), TLR4 (rs4986790, rs4986791), TLR9 (rs5743836, rs187084) and NF-kappa B1 (rs28362491) alleles. The presence of the TLR9 - 1486 T variant (p < 0.0001) and its homozygosity (p < 0.0001) were found to be associated with disease susceptibility. The TLR9 - 1237 C allele was associated with predisposition to RA in females only (p = 0.005). Moreover, the TLR4 rs4986791 G (rs4986790 T) alleles were more frequently detected among patients with the stage IV disease (p = 0.045), and were associated with more effective response to anti-TNF-alpha therapy (p = 0.012). More efficient response to anti-TNF-alpha treatment was also observed in patients with del within the NF-kappa B1 gene (p = 0.047), while for the TLR9 - 1486 T homozygotes, the treatment was ineffective (p = 0.018). TLR polymorphisms affect disease susceptibility and response to therapy with TNF-alpha inhibitors in RA patients of Caucasian origin.
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