Association between anti-tumour necrosis factor treatment response and genetic variants within the TLR and NFκB signalling pathways

Potter, Catherine; Cordell, Heather J.; Barton, Anne; Daly, Ann K.; Hyrich, KL; Mann, Derek A.; Morgan, Ann W; Ag, Wilson; Isaacs, John D.

doi:10.1136/ard.2009.117309

Cited by 77 publications

(48 citation statements)

References 25 publications

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“…There are only a few studies of the presence or functional role of this polymorphism in human disorders. MyD88 rs7744 has been associated with autoimmune or inflammatory processes, [52][53][54] but its biological function has not yet been identified. As it is located in the 3' untranslated region (UTR) region, MyD88 rs7744 could influence the stability of mRNA, thereby compromising normal protein levels.…”

Section: E53mentioning

confidence: 99%

Evidence of activation of the Toll-like receptor-4 proinflammatory pathway in patients with schizophrenia

García‐Bueno

Gassó

MacDowell

et al. 2016

jpn

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Section: E53mentioning

confidence: 99%

Evidence of activation of the Toll-like receptor-4 proinflammatory pathway in patients with schizophrenia

García‐Bueno

Gassó

MacDowell

et al. 2016

jpn

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“…In addition, this minor allele homozygote was associated with the disease severity of UC, hospitalization and response to steroid treatment. Potter et al have reported that rs7744 is nominally associated with a response to anti-TNF therapy for rheumatoid arthritis (29). This evidence indicates that rs7744 may be associated with a response to treatment for UC.…”

Section: ------------------------------------------------------------mentioning

confidence: 84%

The *1244 A>G polymorphism of MyD88 (rs7744) is closely associated with susceptibility to ulcerative colitis

Matsunaga

Tahara

Shiroeda

et al. 2013

Molecular Medicine Reports

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Abstract. Toll-like receptor activation intitially recruits the myeloid differentiation primary response gene (88) (MyD88) protein. A polymorphism *1244 A>G (rs7744) in the 3'-untranslated region of MyD88 has been identified. In the present study, the association of this polymorphism with ulcerative colitis (UC) was investigated. The population studied comprised 922 individuals, including patients with UC (UC cases) and without (controls). Genotyping of rs7744 was performed by PCR single-strand conformation polymorphism and the rs7744 G allele frequencies in the controls and UC cases were 32.8 and 43.5%, respectively (P<0.0001). The results showed that the genotype frequency of the AA homozygote was significantly lower and that of the GG homozygote was significantly higher in the UC cases compared with those in the controls (P=0.0012 for both groups). The rs7744 minor allele variants were significantly associated with susceptibility to UC as indicated by dominant and recessive genetic models. The minor allele variants were associated with an increased risk for UC in the male individuals but not the female individuals. The rs7744 was also associated with a non-continuous phenotype of UC and steroid unused/independent UC. This minor allele homozygote was associated with the disease severity of UC, hospitalization and response to steroid treatment. The results of the present study provided evidence that MyD88 polymorphism rs7744 was significantly associated with the development of UC and that this polymorphism may be associated with the response to treatment therapies for

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“…SNPs located within the TLR and NF-ĸB pathways such as rTLR signalling protein MyD88 (rs7744) and kinase CHUK (rs11591741) have been demonstrated to be associated with good response to anti-TNF therapy [36]. MyD88 and CHUK play integral roles in the NFĸB signalling system, effecting TNF production and chronic inflammatory processes [37,38].…”

Section: Theranostic Biomarkers and Response To Anti-tnf Therapymentioning

confidence: 99%

Diagnostic, Prognostic and Theranostic Biomarkers for Rheumatoid Arthritis

McGeough

Bjourson²

2013

J Clin Cell Immunol

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The identification and adoption of diagnostic and prognostic biomarkers for rheumatoid arthritis has informed and improved the clinical management of this disease. With the advent of biologic treatments such as anti-Tumour Necrosis Factor (anti-TNF) therapy, achieving disease remission has become a realistic endpoint for clinicians. The life-changing efficacy of these therapies however is restricted to the 60-70% of patients who respond. The immune reaction to anti-inflammatory therapy is thought to be influenced by many genes which cumulatively contribute to a threshold for response. There is an inherent clinical need to provide theranostic biomarkers which could determine treatment outcome. The current role of genetic biomarkers in diagnosis, prognosis and predicting response to anti-TNF therapy are discussed.

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Association between anti-tumour necrosis factor treatment response and genetic variants within the TLR and NFκB signalling pathways

Abstract: Several SNPs mapping to the TLR and NFkappaB signalling systems demonstrated association with anti-TNF response as a whole and, in particular, with response to etanercept. Validation of these findings in an independent cohort is now warranted.

Cited by 77 publications

References 25 publications

Evidence of activation of the Toll-like receptor-4 proinflammatory pathway in patients with schizophrenia

Evidence of activation of the Toll-like receptor-4 proinflammatory pathway in patients with schizophrenia

The *1244 A>G polymorphism of MyD88 (rs7744) is closely associated with susceptibility to ulcerative colitis

Diagnostic, Prognostic and Theranostic Biomarkers for Rheumatoid Arthritis

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