Association of Toll like receptor Asp299Gly with rheumatoid arthritis risk: A systematic review of case–control studies and meta-analysis

Tizaoui, Kalthoum; Naouali, Abir; Kaabachi, Wajih; Hamzaoui, A.; Hamzaoui, Kamel

doi:10.1016/j.prp.2014.11.001

Cited by 8 publications

(9 citation statements)

References 48 publications

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“…In the present study, both the TLR4 rs4986790 and rs4986791 were found to be not polymorphismic, which was similar with the previous results reported by Zheng et al [14], Yuan et al [35], and Kang et al [36]. In addition, no significant association between the TLR4 rs4986790 and rs4986791 polymorphisms and RA risk was identified by metaanalysis [37][38]. Thus, we may conclude that the TLR4 rs4986790 and rs4986791 did not contribute to the pathogenesis of RA.…”

Section: Discussionsupporting

confidence: 91%

WITHDRAWN: The genetic association between TLR-1, -2, -4, and -6 gene polymorphisms and rheumatoid arthritis (RA) susceptibility in a Chinese Han population

Peng¹,

Chen²,

Sheng³

et al. 2020

Preprint

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Background: The toll-like receptor (TLR) genes were shown to be involved in the pathogenesis of RA. We aimed to investigate the genetic associations between the TLR-1, -2, -4, and -6 genes polymorphisms and RA susceptibility in a Chinese Han population. Methods : Six polymorphisms (TLR-1 (rs5743610, rs5743618), -2 (rs5743708), -4 (rs4986790, rs4986791), and -6 (rs5743810)) in TLRs genes were genotyped in 360 patients with RA and 560 matched healthy controls by using direct sequencing method. The ORs and 95% CIs were evaluated using a standard logistic regression analysis. Results : No significant association between the allelic, dominant and recessive models of TLR-1 rs5743618, TLR-2 rs5743708, TLR-4 rs4986790 and rs4986791, and TLR-6 rs5743810 polymorphisms and RA risk was observed (p>0.05). However, significant associations were detected between the allelic, dominant and recessive models of TLR-1 rs5743618 and RA risk (allelic: OR[95%CI]= 2.21 [1.73, 2.81], p<0.0001; dominant: OR[95%CI]= 2.33 [1.75, 3.09], p<0.0001; recessive models: OR[95%CI]= 3.70 [1.85, 7.41], p=0.0002), In addition, the TLR6 rs5743810 was found to be associated with the RF - and anti-CCP - antibody in RA group (RF: OR[95%CI]= 2.29 [1.42, 3.69], p=0.0007; anti-CCP: OR[95%CI]= 2.33 [1.39, 3.89], p=0.001). Conclusions : The allelic, dominant, and recessive models of TLR1 rs5743618 might be associated with RA susceptibility. And the TLR6 rs5743810 might be associated with RF and anti-CCP antibody in RA in Chinese Han population.

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Section: Discussionsupporting

confidence: 91%

WITHDRAWN: The genetic association between TLR-1, -2, -4, and -6 gene polymorphisms and rheumatoid arthritis (RA) susceptibility in a Chinese Han population

Peng¹,

Chen²,

Sheng³

et al. 2020

Preprint

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“…Some potential associations of polymorphic variants of the genes coding for TLRs with RA susceptibility in various populations have been described [ 12 , 13 , 14 ]. A relationship between TLR 3 rs3775291 genetic variants and sero-negative RA has been reported in Caucasian population from Denmark [ 12 ].…”

Section: Discussionmentioning

confidence: 99%

“…The TLR4 polymorphism resulting in the Asp299Gly amino acid substitution (rs4986790) did not appear to affect susceptibility to RA in UK patients [ 15 ], nor in 5 other European studies [ 16 ], which also concurs with our current observations. Additionally, a recently published meta-analysis did not show any significant association of this SNP with predisposition to RA [ 14 ].…”

Section: Discussionmentioning

confidence: 99%

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

Gębura

Świerkot

Wysoczańska

et al. 2017

IJMS

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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 TLR2, TLR4, TLR9 and NF-κB1 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 TLR2 (rs111200466), TLR4 (rs4986790, rs4986791), TLR9 (rs5743836, rs187084) and NF-κB1 (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-α therapy (p = 0.012). More efficient response to anti-TNF-α treatment was also observed in patients with del within the NF-κB1 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-α inhibitors in RA patients of Caucasian origin.

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“…Surprisingly, relatively few genetic studies reported significant associations of polymorphisms in TLR4 with RA and JIA susceptibility. Most studies have focused on the correlation between two well known TLR4 polymorphisms (Asp299Gly and Thr399Ile) and RA and JIA, while inconclusive or contradictory results were observed [ 20 , 21 ]. To our knowledge, only three studies with relatively small sample size have investigated the association between variants in the TLR4 and RA in Chinese Han population [ 22 – 24 ], and negative result was also reported [ 23 , 24 ].…”

Section: Introductionmentioning

confidence: 99%

TLR4 rs41426344 increases susceptibility of rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA) in a central south Chinese Han population

Wang

Chen

et al. 2017

Pediatr Rheumatol

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BackgroundThe aim of the study was to determine whether polymorphisms in toll-like receptor 4 (TLR4) confer susceptibility to rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA) in a central south Chinese Han population.MethodsGenotyping for six well studied polymorphisms (rs4986790, rs4986791, rs10759932, rs41426344, rs11536889 and rs7873784) in TLR4 gene were conducted in 1074 unrelated patients with RA and 1692 healthy control subjects, as well as in 217 unrelated patients with JIA and 378 healthy control subjects using direct sequencing technique. Comparisons between cases and controls in alleles, genotypes and haplotypes were carried out using Fisher’s exact test.ResultsSignificant genetic associations were detected between the 3’UTR rs41426344C and RA (p < 0.001, p adj < 0.001, OR = 2.24) and JIA (p < 0.001, p adj < 0.001, OR = 2.05). In addition, rs4986790G was found to be significantly associated with the susceptibility for RA (p = 0.005, p adj = 0.03, OR = 3.43), but not for JIA (p = 0.06, p adj = 0.36, OR = 2.65). Furthermore, significant increasing in the distributions of haplotypes H4 and H10 in RA (H4: p = 0.001, OR = 1.13; H10: p = 0.001, OR = 1.15) and JIA (H4: p = 0.04, OR = 2.06; H10: p = 0.02, OR = 2.47) were also found. Moreover, the frequency of rs41426344C significantly increased in RF-positive and anti-CCP positive subjects both in RA (RF+: p <0.0001, OR = 2.33; anti-CCP+: p =0.008, OR = 2.79) and JIA (RF+: p =0.02, OR = 2.91; anti-CCP+: p = 0.02, OR = 2.78).ConclusionsOur study suggested that rs41426344 and rs4986790 of TLR4 might contribute to RA, and rs41426344 might contribute to JIA pathogenesis in central south Chinese Han population.Electronic supplementary materialThe online version of this article (doi:10.1186/s12969-017-0137-5) contains supplementary material, which is available to authorized users.

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Association of Toll like receptor Asp299Gly with rheumatoid arthritis risk: A systematic review of case–control studies and meta-analysis

Cited by 8 publications

References 48 publications

WITHDRAWN: The genetic association between TLR-1, -2, -4, and -6 gene polymorphisms and rheumatoid arthritis (RA) susceptibility in a Chinese Han population

WITHDRAWN: The genetic association between TLR-1, -2, -4, and -6 gene polymorphisms and rheumatoid arthritis (RA) susceptibility in a Chinese Han population

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

TLR4 rs41426344 increases susceptibility of rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA) in a central south Chinese Han population

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