NOD2, CD14 and TLR4 mutations do not influence response to adalimumab in patients with Crohn's disease: a preliminary report

Acosta, Manuel Barreiro‐de; Ouburg, Sander; Morré, Servaas A.; Crusius, J. Bart A.; Lorenzo, Aurelio; Potel, J; Salvador-Peña, A.; Domínguez‐Muñoz, J. Enrique

doi:10.4321/s1130-01082010001000005

Cited by 14 publications

(7 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, rs5744168 in TLR5 and rs12377632 in TLR4 did not show any association with response [ 23 ]. A study on patients with CD with adalimumab, focused on genetic variants in CD14 and TLR4 was not able to replicate the above findings [ 42 ].…”

Section: Polymorphisms Associated With Response To Anti-tnf Drugs mentioning

confidence: 99%

Association between Genetic Polymorphisms and Response to Anti-TNFs in Patients with Inflammatory Bowel Disease

Prieto-Pérez

Almoguera

Cabaleiro

et al. 2016

IJMS

View full text Add to dashboard Cite

Tumor necrosis factor (TNF) α is a major proinflammatory cytokine involved in the immune response in inflammatory bowel disease (IBD). Anti-TNF drugs such as infliximab and adalimumab are used to treat IBD; however, approximately 30% of patients do not respond to treatment. Individual genetic differences could contribute to lack of efficacy. Genetic studies have tried to uncover the factors underlying differences in response, however, knowledge remains limited, and the results obtained should be validated, so that pharmacogenetic information can be applied in clinical practice. In this review, we gather current knowledge in the pharmacogenetics of anti-TNF drugs in patients with IBD. We observed a connection between the major genes described as possible predictors of response to anti-TNF drugs in IBD and the cytokines and molecules involved in the T helper (Th) 17 pathway.

show abstract

Section: Polymorphisms Associated With Response To Anti-tnf Drugs mentioning

confidence: 99%

Association between Genetic Polymorphisms and Response to Anti-TNFs in Patients with Inflammatory Bowel Disease

Prieto-Pérez

Almoguera

Cabaleiro

et al. 2016

IJMS

View full text Add to dashboard Cite

show abstract

“…However, they showed that the presence of ACPA did not affect the response to adalimumab in -308 TNF-α G/G genotype patient. Another study demonstrated that the polymorphisms in NOD2, CD14 and Toll-like receptor (TLR) 4 genes did not influence the response to adalimumab in patients with CD [56]. However, Potter et al [57] reported that several SNPs mapping to the TLR and NFκB as MyD88 and CHUK were associated with the response particularly to etanercept.…”

Section: Pharmacogeneticsmentioning

confidence: 99%

Pharmacogenetics: Reality or Dream in Predicting the Response to TNF-α Inhibitor Treatment?

Murdaca¹

2013

J Genet Syndr Gene Ther

View full text Add to dashboard Cite

Background: The ongoing progresses in the knowledge of the pathogenic mechanisms of various immunemediated or inflammatory diseases such as rheumatoid arthritis, systemic lupus erythematosus, Crohn's disease, ankylosing spondylitis, disseminated granuloma annulare, psoriasis and/or psoriatic arthritis, and the availability of innovative biotechnological approaches have lead to the development of new drugs which add to conventional treatments. There are five TNF-α inhibitors available for clinical use including anti-TNF-α monoclonal antibodies (infliximab, adalimumab, golimumab and certolizumab pegol) and a fusion protein that acts as a "decoy receptor" for TNF-α (etanercept). Pharmacogenetics has the potential of increasing drug efficiency by identifying genetic factors responsible for lack response or toxicities to TNF-α inhibitors. Methods: We analyzed the most recent studies in the literature relating to different genetic polymorphisms and their potential association with the therapeutic response to TNF-α inhibitors. Results: SNP at position-308 of the TNF-α promoter genes and particularly the-308 G/G genotype and HLA-DRB1-encoding shared epitope (allele *0404 and allele *0101) may predict a better response to etanercept. Polymorphisms of TNFR1 and TNFR2 decrease response to infliximab. By contrast, FCGR3A-158 polymorphism seems to favor the response to infliximab. G allele of SNP rs610604 located in the TNFAIP3 gene and its haplotype with the T allele of rs2230926 could be considered as markers of good response to etanercept, infliximab and adalimumab. Conclusion: Most of these studies are often small and not sufficiently powered to detect an effect and often examines only the effects of a single SNP, while it would be more useful to analyze more haplotypes in contemporary in the same patients. Candidate genes may be in linkage with other loci, thus, having a true influence upon the pharmacology of TNF-α inhibitors. Further studies are needed before a pharmacogenetic approach may be applicable in daily clinical therapeutic practice.

show abstract

“…It is a key molecule that reacts to the intracellular presence of peptidoglycans of bacterial origin [13]. The binding of peptidoglycans initiates the signalling cascade, ending with NF-κB activation and the expression of pro-inflammatory genes including TNFα [14,15]. In the gene for the protein NOD2, several polymorphisms were described.…”

Section: Nod2/card15 Genementioning

confidence: 99%

“…Factors which quantitatively influence the TNFα expression as well as molecules, which are inductors of this expression, seem to be potential predictors of the therapeutic response to biological therapy. One of the key molecules which regulate the gene expression of many cytokines is the nuclear factor κB (NF-κB) [14,15]. Its activation is closely linked with complex intracellular processes, by which the immune system recognizes bacterial antigens and reacts to their presence.…”

Section: Polymorphisms Which Influence the Anti-tnfα Antibodies Therapymentioning

confidence: 99%

“…They are molecules, which participate in the activation of NF-κB, the inductor of the TNFα expression. Nuclear factor κB (NF-κB) is a key component in the regulation of expression in the area of genome-carrying genes for cytokines [14,15]. Its activation is closely connected with complex intracellular processes, by which the immune system responds to the presence of bacterial antigens.…”

Section: Gene Polymorphisms As Predictors Of the Effectiveness Of Infmentioning

confidence: 99%

See 1 more Smart Citation

Gene Polymorphisms and Inflammatory Bowel Diseases

Bartošová¹,

Kolorz²,

Wroblova³

et al. 2012

Inflammatory Bowel Disease

View full text Add to dashboard Cite

NOD2, CD14 and TLR4 mutations do not influence response to adalimumab in patients with Crohn's disease: a preliminary report

Cited by 14 publications

References 29 publications

Association between Genetic Polymorphisms and Response to Anti-TNFs in Patients with Inflammatory Bowel Disease

Association between Genetic Polymorphisms and Response to Anti-TNFs in Patients with Inflammatory Bowel Disease

Pharmacogenetics: Reality or Dream in Predicting the Response to TNF-α Inhibitor Treatment?

Gene Polymorphisms and Inflammatory Bowel Diseases

Contact Info

Product

Resources

About