类风湿关节炎患者CYP3A4、2C9和2D6基因多态性与艾瑞昔布胃肠道不良反应的相关性研究

Correlation between CYP3A4,2C9 and 2D6 gene polymorphisms and adverse gastrointestinal reactions of imrecoxib in patients with rheumatoid arthritis

目的:探讨代谢酶CYP3A4、2C9和2D6基因多态性与类风湿关节炎(rheumatoid arthritis,RA)患者使用艾瑞昔布期间胃肠道不良反应的相关性。方法:前瞻性收集服用艾瑞昔布的RA患者,记录服药期间的胃肠道反应,采用Mass ARRAY芯片系统检测患者CYP3A4(rs2242480、rs2246709、rs3735451、rs4646437、rs4646440),CYP2C9(rs1934967、rs2253635、rs2475376、rs4918766、rs9325473、rs9332098),CYP2D6(rs1080983)位点的基因型,SPSS 26.0软件统计分析CYP450不同基因型与艾瑞昔布治疗后胃肠道不良反应的相关性。结果:纳入安徽医科大学第一附属医院风湿免疫科2020年2月—2021年2月收治的服用艾瑞昔布的88例RA患者,发生胃肠道反应15例,基因型分布符合Hardy-Weinberg平衡检测。CYP3A4rs4646437 GG型、rs4646440 GG型、rs2242480 CC型、rs3735451 TT型;CYP2C9rs4918766GG、rs2253635CC型胃肠道反应发生率更高。结论:CYP3A4、CYP2C9部分基因型与RA患者服用艾瑞昔布的胃肠道不良反应发生具有一定的相关性。

Objective To explore the association of genetic polymorphisms of metabolic enzymes CYP3A4,2C9 and 2D6 with adverse gastrointestinal reactions during dosing of imrecoxib in patients with rheumatoid arthritis(RA).Methods From February 2020 to February 2021,88 RA patients were hospitalized at First Affiliated Hospital of Anhui Medical University.The incidence of gastrointestinal reactions was recorded.Mass ARRAY chip system was employed for detecting the genetic polymorphisms of CYP3A4(rs2242480,rs2246709,rs3735451,rs4646437&rs4646440),CYP2C9(rs1934967,rs2253635,rs2475376,rs4918766,rs9325473&rs9332098)and CYP2D6(rs1080983).SPSS 26.0 software was utilized for examining the correlations between different genotypes of CYP450 and adverse gastrointestinal reactions after dosing of imrecoxib.Results Among them,15 patients developed gastrointestinal reactions.And the distribution of genotype stayed in Hardy-Weinberg equilibrium.CYP3A4 rs4646437 GG,rs4646440 GG,rs2242480 CC,rs3735451 TT;CYP2C9 rs4918766 GG and rs2253635 CC had a higher incidence of gastrointestinal reactions.Conclusion CYP3A4 and CYP2C9(partial)genotypes are correlated with the occurrence of adverse gastrointestinal reactions in RA patients on imrecoxib.