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| Influence of FCGR3A gene variations on the risk of Crohn’s disease and the clinical response to infliximab in Chinese patients |
| SHAO Xiaoxiao, HU Dingyuan, CAO Shuguang, WU Hao, XU Yuan, HU Yue, JIANG Yi. |
| Department of Gastroenterology, the Second Affiliated Hospital & Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou 325027, China |
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SHAO Xiaoxiao,HU Dingyuan,CAO Shuguang, et al. Influence of FCGR3A gene variations on the risk of Crohn’s disease and the clinical response to infliximab in Chinese patients[J]. JOURNAL OF WEZHOU MEDICAL UNIVERSITY, 2023, 53(3): 173-181.
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Abstract Objective: To investigate the influence of FCGR3A (rs396991, rs4656317) gene variations on the risk of Crohn’s disease (CD) and the clinical response to infliximab (IFX). Methods: After the collection of 225 CD patients and 476 age- and gender-matched controls from the Second Affiliated Hospital & Yuying Children’s Hospital of Wenzhou Medical University during January 2012 to January 2021, the genotypes of rs396991 and rs4656317 were determined by Matrix Assisted Laser Desorption Spectrometry for time-of-flight Mass Spectrometry technique. Linkage disequilibrium (LD) and haplotype were analyzed in all study subjects.Of 225 CD patients, who had initial active stage [Crohn’s disease activity index (CDAI)≥150 points] were given intravenous IFX (5 mg/kg) at week 0, 2, and 6 to induce remission, followed by the same dose of IFX every 8 weeks. These patients were divided into response group and non-response group based on CDAI and simplified endoscopic score for Crohn’s disease (SES-CD) at 14th week. A retrospective analysis was performed for the influence of FCGR3A gene variations on the clinical response of IFX in this cohort of CD patients. Results: The variant allele (C) of rs396991 was shown to be more prevalent in CD patients than in the controls (39.33% vs. 31.83%, P=0.006). Both the variant allele (C) and variant genotype (GC+CC) of rs4656317 were more frequent in CD patients than in the controls (45.33% vs. 36.55%, P=0.002; 71.11% vs. 61.76%, P=0.016). The stratified analysis indicated that the variant genotype (AC+CC) of rs396991 and variant genotype (GC+CC) of rs4656317 were decreased in the patients with type L2 CD or type L3 CD in contrast to those with type L1 CD (55.00% vs. 72.31%, P=0.016; 66.25% vs. 83.08%, P=0.012). The polymorphic loci of rs396991 and rs4656317 were in close linkage disequilibrium with each other in FCGR3A gene (D’=0.94, r2=0.72). The analysis for LD showed that the frequency of haplotype (AG) was lower in CD patients than in the controls (53.78% vs. 62.18%, P=0.003).In contrast, the frequency of haplotype (CC) was higher in CD patients than in the controls (38.67% vs. 30.56%,P=0.003). After the treatment of IFX for 14 weeks, 98 CD patients with initial active stage were divided into response group (82 cases) and non-response group (16 cases). The variant allele (C) of rs396991 was shown to be less prevalent in response group than in non-response group (23.17% vs. 43.75%, P=0.016). At the 14th week, 16 patients of non-response group were analyzed according to the effective concentration of IFX and the concentration of IFX anti-antibody. The result suggested that the proportion of rs396991 allele C in IFX anti-antibody highconcentration group (≥70 ng/mL) was higher than that in IFX anti-antibody low-concentration group (<70 ng/mL) (71.43% vs. 22.22%, P=0.011). Conclusion: Both the variations of rs396991 and rs4656317 in FCGR3A gene may increase the risk of CD, especially the risk of terminal ileal involvement. In addition, the variation of rs396991 might contribute to the production of IFX anti-antibody, thereby reducing the clinical response of CD patients to IFX treatment.
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Received: 08 December 2022
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