[Relationships of interleukin-7 receptor gene polymorphisms with the risk of Crohn's disease and the efficacy of infliximab].

Objectives: To explore the relationships of interleukin-7 receptor (IL-7R) gene polymorphisms with the risk of Crohn's disease (CD), as well as the efficacy of infliximab (IFX) in patients with CD. Methods: The CD patients (CD group) and healthy controls (control group) at the Second Affiliated Hospital of Wenzhou Medical University between January 2020 and May 2025 were retrospectively collected. Genotypes of IL-7R gene at loci rs6897932, rs1494555, rs1494558 were examined in both groups. According to Montreal CD Classification, the disease locations were divided into terminal ileal-type, colonic-type, ileocolic-type and upper gastrointestinal-type. Among CD patients receiving IFX treatment, the clinical response was evaluated by Crohn's Disease Activity Index (CDAI) at week 14 of follow-up. The patients were divided into the clinical response group (a decline of CDAI≥100 points compared with week 0) and the clinical non-response group. The efficacy of endoscopy was assessed by Simplified Endoscopic Score for Crohn's Disease (SES-CD) at week 32. The patients were divided into the mucosal healing group (SES-CD≤2 points or absence of mucosal ulcerations) and the mucosal non-healing group. The distribution differences of IL-7R gene polymorphisms were compared between CD group and control group, among CD patients with different clinical phenotypes, between the clinical response group and the clinical non-response group, as well as between the mucosal healing group and the mucosal non-healing group. The genotypes or alleles with distribution differences were included into multivariate logistic regression model to investigate the relationships of IL-7R gene polymorphisms with the risk of CD, the clinical phenotypes, and the clinical efficacy of IFX in CD patients. Results: The CD group consisted of 303 participants [200 males and 103 females, aged 30 (23, 40) years]. The control group consisted of 514 participants [313 males and 201 females, aged 32 (26, 42) years]. The variant allele (T) [14.0% (85/606) vs 18.5% (190/1 028)] of locus rs6897932 were less frequent in the CD group than that in the control group, but the difference was not statistically significant after adjustment (adjusted P=0.054). The homozygous variant genotype (TT) of locus rs6897932 in the patients with terminal ileal-type and ileocolic-type CD group were less frequent than that with colonic-type CD [0.8% (2/261) vs 9.5% (4/42), adjusted P=0.009]. The homozygous variant genotype (TT) of locus rs6897932 (OR=0.06, 95%CI: 0.01-0.38) was the related factor influencing the terminal ileum involvement (the disease location is terminal ileal-type or ileocolic-type) in CD patients. A total of 112 CD patients were treated with IFX. There were 78 cases in the clinical response group and 34 cases in the clinical non-response group at week 14 of IFX treatment. The variant genotype (CT+TT) [38.5% (30/78) vs 11.8% (4/34), adjusted P=0.015] and variant allele (T) [20.5% (32/156) vs 5.9% (4/68), adjusted P=0.018] of locus rs6897932 in the clinical response group were more frequent than those in the clinical non-response group. The variant genotype (CT+TT) (OR=5.17, 95%CI: 1.54-17.36) of locus rs6897932 was the related factor influencing the clinical response at week 14. There were 43 cases in the mucosal healing group and 69 cases in the mucosal non-healing group at week 32 of IFX treatment. The variant genotype (TC+CC) [65.1% (28/43) vs 85.5% (59/69), adjusted P=0.036] of locus rs1494558 in the mucosal healing group was less frequent than that in the mucosal non-healing group. The variant genotype (TC+CC) (OR=0.24, 95%CI: 0.09-0.71) of locus rs1494558 was the related factor influencing the mucosal healing at week 32. Conclusions: The homozygous variant genotype (TT) of locus rs6897932 in IL-7R gene may be related with a lower risk of terminal ileum involvement (the disease location is terminal ileal-type or ileocolic-type). In CD patients receiving IFX treatment, the variant genotype (CT+TT) of locus rs6897932 in IL-7R gene may be related with an increased clinical response rate at week 14, while the variant genotype (TC+CC) of locus rs1494558 may be related with a reduced mucosal healing rate at week 32.