甲氨蝶呤代谢酶基因多态性与类风湿关节炎患者疗效的相关性研究  

Correlation between Gene Polymorphisms of Metabolic Enzymes and Therapeutic Effect of Methotrexate for Rheumatoid Arthritis

作　　者：束庆[1] 曹智 王丹丹[3] 朱怀军[1] 葛泳含 刘蕴星 姚瑶[1] 孙雷 葛卫红[1] SHU Qing;CAO Zhi;WANG Dandan;ZHU Huaijun;GE Yonghan;LIU Yunxing;YAO Yao;SUN Lei;GE Weihong(Department of Pharmacy,the Affiliated Drum Tower Hospital of Nanjing University Medical School,Nanjing,Jiangsu 210008;Department of Pharmacy,the Affiliated Pizhou Hospital of Xuzhou University Medical School,Xuzhou,Jiangsu 221300;Department of Rheumatology and Immunology,the Affiliated Drum Tower Hospital of Nanjing University Medical School,Nanjing,Jiangsu 210008)

机构地区：[1]南京大学医学院附属鼓楼医院药学部,南京210008 [2]徐州医科大学附属邳州医院药学部,徐州221300 [3]南京大学医学院附属鼓楼医院风湿免疫科,南京210008

出　　处：《药学与临床研究》2020年第6期401-407,共7页Pharmaceutical and Clinical Research

基　　金：江苏省医学创新团队项目(CXTDA2017041);南京市医学科技发展资金项目(QRX17140);国家自然科学基金项目(81603087);江苏省药学会—奥赛康医院药学科研项目(A201704);南京鼓楼医院新技术发展基金项目(XJSFZJJ201806)。

摘　　要：目的:研究参与甲氨蝶呤(MTX)代谢酶的基因多态性与中国类风湿关节炎(RA)患者疗效的相关性。方法:采用队列研究设计法,共纳入符合RA诊断并服用MTX的患者109例,按照入组标准分为有效组和无效组:有效组患者[稳定剂量的MTX治疗至少6个月、血细胞沉降率(ESR)<20 mm·h^-1];无效组患者(稳定剂量的MTX治疗至少3个月,ESR改善低于20%)。采用聚合酶链式反应限制性片段长度多态性分析技术,测定患者样本的RFC-1(rs1051266)、ABCB1(rs1045642)、MTHFR(rs1801131,rs1801133)、TYMS(rs2853542)、ATIC(rs2372536、rs12995526、rs3821353、rs7563206、rs16853834)、DHFR(rs408626、rs12517451、rs10072026、rs1643657)等的基因型。结果:TYMS(rs34743033)的基因型分布(2R2R/2R3R/3R3R)在有效组和无效组中进行纯合突变型(2R2R)与杂合基因型+野生基因型(2R3R+3R3R)进行χ2检验后得到的P值有统计学差异(χ^2=5.69,P=0.02)。结论:TYMS(rs34743033)的基因多态性可能影响RA患者对MTX的疗效反应,TYMS(rs34743033)含有三个重复序列的患者可预测使用MTX治疗6个月后有较好的疗效。Objective:To investigate the correlation of metabolic enzymes gene polymorphisms of methotrexate(MTX)and its therapeutic effect in Chinese rheumatoid arthritis(RA)patients.Methods:A total of 109 RA patients treated with MTX were enrolled in our study.Their responses to MTX were rated within erythrocyte sedimentation rates(ESR).According to the reducing rates of ESR,the patients were divided into two groups:effective group(stable doses of MTX therapy for at least 6 months,ESR<20 mm·h^-1)and ineffective group(stable doses of MTX therapy for at least 3 months,ESR improvement<20%).The subjects'genetic loci RFC-1(rs1051266),ABCB1(rs1045642),MTHFR(rs1801131,rs1801133),TYMS(rs2853542),ATIC(rs2372536,rs12995526,rs3821353,rs7563206,rs16853834)and DHFR(rs408626,rs12517451,rs10072026,rs1643657)were tested through PCR-RFLP.Results:There was a significant difference between 2R2R and 2R3R+3R3R of TYMS(rs34743033),χ^2=5.69,P=0.02.Conclusion:RA patients with 3R genetic loci of TYMS(rs34743033)may predict better treatment of MTX for 6 months.

关 键 词：甲氨蝶呤 基因多态性 类风湿关节炎 疗效 

分 类 号：R969.1[医药卫生—药理学]