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Polymorphisms within Genes Involved in Regulation of the NF-?B Pathway in Patients with Rheumatoid Arthritis.


ABSTRACT: Genes involved in regulation of the nuclear factor-?B (NF-?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-?B1 genes were investigated to assess their associations with RA susceptibility, progression and response to anti-TNF-? therapy. A group of 110 RA patients and 126 healthy individuals were genotyped for TLR2 (rs111200466), TLR4 (rs4986790, rs4986791), TLR9 (rs5743836, rs187084) and NF-?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-? therapy (p = 0.012). More efficient response to anti-TNF-? treatment was also observed in patients with del within the NF-?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-? inhibitors in RA patients of Caucasian origin.

SUBMITTER: Gebura K 

PROVIDER: S-EPMC5535923 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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Polymorphisms within Genes Involved in Regulation of the NF-κB Pathway in Patients with Rheumatoid Arthritis.

Gębura Katarzyna K   Świerkot Jerzy J   Wysoczańska Barbara B   Korman Lucyna L   Nowak Beata B   Wiland Piotr P   Bogunia-Kubik Katarzyna K  

International journal of molecular sciences 20170704 7


Genes involved in regulation of the nuclear factor-κB (NF-κB)-pathway are suggested to play a role in pathogenesis of rheumatoid arthritis (RA). In the present study, genetic polymorphisms of <i>TLR2</i>, <i>TLR4</i>, <i>TLR9</i> and <i>NF-κB1</i> genes were investigated to assess their associations with RA susceptibility, progression and response to anti-TNF-α therapy. A group of 110 RA patients and 126 healthy individuals were genotyped for <i>TLR2</i> (rs111200466), <i>TLR4</i> (rs4986790, rs  ...[more]

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