In:
Alimentary Pharmacology & Therapeutics, Wiley, Vol. 49, No. 7 ( 2019-04), p. 890-903
Abstract:
Anti‐tumor necrosis factor‐α ( TNF ‐α) is used for the treatment of severe cases of IBD , including Crohn's disease ( CD ) and ulcerative colitis ( UC ). However, one‐third of the patients do not respond to the treatment. We have previously investigated whether single nucleotide polymorphisms ( SNP s) in genes involved in inflammation were associated with response to anti‐ TNF therapy among patients with CD or UC . Aim A new cohort of patients was established for replication of the previous findings and to identify new SNP s associated with anti‐ TNF response. Methods Fifty‐three SNP s assessed previously in cohort 1 (482 CD and 256 UC patients) were genotyped in cohort 2 (587 CD and 458 UC patients). The results were analysed using logistic regression (adjusted for age and gender). Results Ten SNP s were associated with anti‐ TNF response either among patients with CD ( TNFRSF 1A (rs4149570) ( OR : 1.92, 95% CI : 1.02‐3.60, P = 0.04), IL 18 (rs187238) ( OR : 1.35, 95% CI : 1.00‐1.82, P = 0.05), and JAK 2 (rs12343867) ( OR : 1.35, 95% CI : 1.02‐1.78, P = 0.03)), UC ( TLR 2 (rs11938228) ( OR : 0.55, 95% CI : 0.33‐0.92, P = 0.02), TLR 4 (rs5030728) ( OR : 2.23, 95% CI : 1.24‐4.01, P = 0.01) and (rs1554973) ( OR : 0.49, 95% CI : 0.27‐0.90, P = 0.02), NFKBIA (rs696) ( OR : 1.45, 95% CI : 1.06‐2.00, P = 0.02), and NLRP 3 (rs4612666) ( OR : 0.63, 95% CI : 0.44‐0.91, P = 0.01)) or in the combined cohort of patient with CD and UC ( IBD ) ( TLR 4 (rs5030728) ( OR : 1.46, 95% CI : 1.01‐2.11, P = 0.04) and (rs1554973)( OR : 0.80, 95% CI : 0.65‐0.98, P = 0.03), NFKBIA (rs696) ( OR : 1.25, 95% CI : 1.01‐1.54, P = 0.04), NLRP 3 (rs4612666) ( OR : 0.73, 95% CI : 0.57‐0.95, P = 0.02), IL 1 RN (rs4251961) ( OR : 0.81, 95% CI : 0.66‐1.00, P = 0.05), IL 18 (rs1946518) ( OR : 1.24, 95% CI : 1.01‐1.53, P = 0.04), and JAK 2 (rs12343867) ( OR : 1.24, 95% CI : 1.01‐1.53, P = 0.04)). Conclusions The results support that polymorphisms in genes involved in the regulation of the NF κB pathway ( TLR 2 , TLR 4, and NFKBIA ), the TNF ‐α signalling pathway ( TNFRSF 1A ), and other cytokine pathways ( NLRP 3, IL 1 RN , IL 18, and JAK 2 ) were associated with response to anti‐ TNF therapy. Our multi‐ SNP model predicted response rate of more than 82% (in 9% of the CD patients) and 75% (in 15% of the UC patients), compared to 71% and 64% in all CD and UC patients, respectively. More studies are warranted to predict response for use in the clinic.
Type of Medium:
Online Resource
ISSN:
0269-2813
,
1365-2036
DOI:
10.1111/apt.2019.49.issue-7
Language:
English
Publisher:
Wiley
Publication Date:
2019
detail.hit.zdb_id:
2003094-0
SSG:
15,3
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