Pharmacogenetic analysis of canonical versus noncanonical pathway of NF-kB in Crohn's disease patients under anti-tumor necrosis factor-α treatment. Issue 6 (22nd June 2022)

• Record Type: Journal Article
• Authors: Stavrou, Eleana F.; Chatzopoulou, Fani; Antonatos, Charalabos; Pappa, Panagiota; Makridou, Eutychia; Oikonomou, Konstantinos; Kapsoritakis, Andreas; Potamianos, Petros S.; Karmiris, Konstantinos; Tzathas, Charalambos; Chatzidimitriou, Dimitris; Vizirianakis, Ioannis S.; Vasilopoulos, Yiannis
• Is Part Of: Pharmaocogenetics and genomics. Volume 32:Issue 6(2022)
• Page Start: 235
• Page End: 241
• Publication Date: 2022-06-22
• Subjects: Crohn's disease -- canonical pathway -- noncanonical pathway -- NF-kB -- TLR2 -- LTA -- TLR4 -- MAP3K14/NIK; Pharmacogenetics -- Periodicals; Pharmacogenomics -- Periodicals; Genetic toxicology -- Periodicals; Biomedical genetics -- Periodicals; 615.7
• DOI: 10.1097/FPC.0000000000000471
• Languages: English
• ISSNs: 1744-6872

Abstract

Abstract : Objectives: This study explores the potential of gene polymorphisms in the canonical and noncanonical NF-kB signaling pathway as a prediction biomarker of anti-tumor necrosis factor (TNF)α response in Crohn's patients. Materials and methods: A total of 109 Greek patients with Crohn's disease (CD) were recruited, and the genotype of TLR2 rs3804099, LTA rs909253, TLR4 rs5030728, and MAP3K14/NIK rs7222094 single nucleotide polymorphisms was investigated for association with response to anti-TNFα therapy. Patient's response to therapy was based on the Crohn's Disease Activity Index, depicting the maximum response within 24 months after initiation of treatment. Results: Seventy-three patients (66.7%) were classified as responders while 36 as nonresponders (33.3%). Comparing allelic frequencies between responders and nonresponders, the presence of TLR2 rs3804099 T allele was associated with nonresponse ( P = 0.003), even after stratification by anti-TNFα drugs (infliximab: P = 0.032, adalimumab: P = 0.026). No other association was identified for the rest of the polymorphisms under study. Haplotype analysis further enhanced the association of rs3804099 T allele with loss of response, even though the results were NS ( P = 0.073). Conclusion: Our results suggest that polymorphisms in the canonical NF-kB pathway genes could potentially act as a predictive biomarker of anti-TNFα response in CD.