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Pharmacogenet Genomics ; 32(6): 235-241, 2022 08 01.
Article in English | MEDLINE | ID: mdl-35852914

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.


Subject(s)
Crohn Disease , Adalimumab/genetics , Adalimumab/therapeutic use , Biomarkers , Crohn Disease/drug therapy , Crohn Disease/genetics , Crohn Disease/pathology , Humans , Infliximab/genetics , Infliximab/therapeutic use , NF-kappa B/genetics , NF-kappa B/therapeutic use , Necrosis/drug therapy , Pharmacogenomic Testing , Polymorphism, Single Nucleotide , Toll-Like Receptor 2/genetics , Treatment Outcome , Tumor Necrosis Factor-alpha/genetics
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