基因多态性对类风湿关节炎药物疗效和不良反应影响的研究进展  

Advances of gene polymorphism affecting rheumatoid arthritis drug efficacy and adverse drug reactions

作　　者：张贤政 邰宇[1] 张玲玲[1] 魏伟[1] ZHANG Xian-Zheng;TAI Yu;ZHANG Ling-ling;WEI Wei(Institute of Clinical Pharmacology,Anhui Medical University,Key Lab of Anti-inflammatory and Immune Medicine, Ministry of Education,Anhui Collaborative Innovation Center of Anti-inflammatory and Immune Medicine,Anhui Anti-inflammatory and Immune Medicine Innovation Team,Hefei 230032,China)

机构地区：[1]安徽医科大学临床药理研究所,抗炎免疫药物教育部重点实验室,安徽省高校抗炎免疫药物协同创新中心,安徽省高校抗炎免疫药物创新团队,安徽合肥230032

出　　处：《中国药理学通报》2018年第9期1193-1198,共6页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No81330081,81473223,81673444)

摘　　要：治疗类风湿关节炎(rheumatoid arthritis,RA)的药物主要包括疾病调修抗风湿药物(disease-modifying antirheumatic drugs,DMARDs)、非甾体抗炎药物(nonsteroidal anti-inflammatory drugs,NSAIDs)、生物制剂等。这些药物对于阻止RA病程和预防并发症起着重要作用,但是药物疗效和不良反应在RA患者中存在个体差异。编码药物代谢酶(二氢叶酸还原酶、细胞色素P450酶、N-乙酰转移酶等)、药物转运蛋白(ATP结合盒转运蛋白等)和药物靶点(肿瘤坏死因子-α受体等)的基因存在多态性。药物转运蛋白基因多态性可改变药物的分布、排泄,药物靶标的多态性明显影响药物的敏感性。这些基因多态性会影响药物代谢动力学和药效学,也可能是导致个体间药物疗效和不良反应差异的重要机制。该文系统综述了基因多态性对RA药物疗效和不良反应的影响。Drugs for the treatment of rheumatoid arthritis(RA)include disease-modifying antirheumatic drugs(DMARDs),nonsteroidal anti-inflammatory drugs(NSAIDs)and biological agents,etc.These drugs are critical in preventing the process and complications of RA.However,the outcome of treatment and adverse drug reactions with these drugs in RA patients are different individually.Drug-metabolizing enzymes(dihydrofolate reductase,cytochrome P450enzymes,N-acetyltransferases,and so on.),drug transporters(ATP-binding cassette transporters)and drug targets(tumor necrosis factor-αreceptors)are coded for by variant alleles.The gene polymorphism of drug transporters can change the distribution and excretion of drugs.The polymorphisms of drug target affect significantly drug sensitivity.These gene polymorphisms may influence the pharmacokinetics,pharmacodynamics and side effects of medicine.In this article,we review the genetic polymorphisms that affect the efficacy of drug or the occurrence of adverse drug reactions in RA.

关 键 词：基因多态性 类风湿关节炎 药物 代谢 疗效 不良反应 

分 类 号：R-05[医药卫生] R392.11