基因多态性与药物不良反应相关性研究进展

Research progress in correlation between genetic polymorphism and adverse drug reactions

检索2009至2013年PubMed、Nature数据库、ScienceDirect数据库和中国期刊全文数据库,收集基因多态性与药物不良反应（ADR）相关性研究的期刊文献进行资料提取和分析,就药物代谢酶、转运蛋白、免疫分子、受体的基因多态性与ADR发生的关系进行综述.药物代谢酶主要涉及细胞色素P450 2C9、N-乙酰基转移酶2、尿苷二磷酸葡萄糖醛酸转移酶1A6、亚甲基四氢叶酸还原酶、基质金属蛋白酶9和二氢嘧啶脱氢酶;转运蛋白主要涉及水溶性载体家族22成员2、电压依赖性钙通道γ亚基6、水溶性载体家族6成员12、ATP结合盒转运体B1;免疫分子主要涉及人类白细胞抗原（human lymphocyte antigen,HLA）相关的基因复合体,包括HLA-B、HLA-A和HLA-C;受体主要涉及多巴胺2受体/含锚蛋白重复和激酶域1 Taq IA基因、趋化因子受体3、孤儿核受体NR4A1、孕烷X受体和白细胞介素4受体α.了解基因多态性与ADR的关系有助于实施个体化用药,避免或减少ADR的发生.

PubMed,Nature database,ScienceDirect database and China National Knowledge Infrastructure （from year 2009 to 2013） were searched.The journal articles on correlation between gene polymorphism and adverse drug reactions were collected and analyzed.This article reviews the articles on correlation between adverse drug reactions and pleomorphic gene of metabolic enzymes,transporters,immune molecule and receptors.The metabolic enzymes mainly included cytochrome P450 2C9,N-acetyltransferase 2,uridine diphosphate glucuronosyl transferase 1A6,methylenetetrahydrofolate reductase,matrix metalloproteinase-9 and dihydropyrimidine dehydrogenase.The transporters mainly included solute carrier family 22 member 2,calcium channel,voltage-dependent,gamma subunit 6,solute carrier family 6 member 12,and ATP-binding cassette B1.The immune molecules mainly included human lymphocyte antigen （HLA） for instance HLA-B,HLA-A and HLA-C.The receptors mainly included dopamine 2 receptors/ankyrin repeat and kinase domain containing 1 Taq IA,chemokine receptor 3,orphan nuclear receptor NR4A1,pregnane X receptor and interleukin-4-receptor alpha.Understanding the relationship between gene polymorphism and adverse drug reactions is helpful to facilitate individualized drug administration and avoid or reduce the occurrence of adverse reactions.