Genetic factors, including single-nucleotide variants (SNVs), may modulate disease course and therapeutic efficacy in patients with inflammatory bowel disease (IBD). We investigated the association between four SNVs in cytokine genes and clinical phenotype as well as the response to molecular-targeted drugs in patients with IBD. A total of 197 IBD patients (142 Crohn's disease [CD], 55 ulcerative colitis [UC]) undergoing targeted treatment were enrolled. The SNVs analysed were: TNFA rs1800629 (-308 G>A), TGFB rs1800471 (-codon 10 C>T), IL6 rs1800795 (-174 G>C), and IL10 rs1800896 (-1082 G>A). Biochemical response at 12 months (T12) was defined as C-reactive protein < 5.0 mg/L and faecal calprotectin < 250 μg/g at T12, in the absence of ongoing corticosteroid therapy. Among the SNVs analysed, the IL6 rs1800795 C allele was significantly associated with a younger age at diagnosis (p = 0.049), while the TNFA rs1800629 A allele was more frequently observed in patients with CD than in UC (p = 0.036). Regarding treatment response, 134 patients completed 12 months of molecular-targeted therapy and were included in the per-protocol analysis; 41.0% achieved biochemical remission at T12. The IL10 rs1800896 variant allele was significantly associated with remission (OR = 2.15, 95% CI: 1.03-4.44; p = 0.041). This association remained significant in multivariate analysis (aOR = 4.15, 95% CI: 1.49-11.56; p = 0.007), independently of clinical and treatment-related variables. In conclusion, genotyping of cytokine-related SNVs may help identify patients with a more aggressive disease phenotype and guide personalised treatment strategies in patients with IBD.
Keywords: Crohn's disease; adalimumab; cytokine; inflammatory bowel disease; infliximab; single‐nucleotide genetic variants; tofacitinib; ulcerative colitis; ustekinumab; vedolizumab.
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