CAJ | 학술논문

细胞色素P450(cytochrome P450,CYP)在众多外源性和内源性物质的代谢中具有重要作用.CYP家族1-3中编码P450的基因均存在多态性,特别是CYP2C9、CYP2C19、CYP2D6和CYP3A5.超过一半的临床药物是由多态性P450介导代谢,CYP基因的多态性是造成药物反应个体差异的主要原因.近几年,许多与P450酶活性和CYP基因表达相关的等位基因已被鉴定,因此通过分型CYP基因的功能性或标签(Tag)的遗传变异,就可以获得个体的代谢表型,有助于医生及时找到正确的用药方案,有效地提高药物疗效和降低毒副作用,特别是那些治疗指数窄的药物.显然,了解CYP基因的遗传变异对于临床药物治疗和药物开发是必不可少的.基因芯片技术具有高多重水平和高通量的特点,使同时分型大量CYP基因遗传变异成为可能,是实现个性化医疗的重要技术保障.然而,DNA制备制约了预测性CYP基因分型芯片的发展,其在临床上的广泛应用尚需时日.
세포색소P450(cytochrome P450,CYP)재음다외원성화내원성물질적대사중구유중요작용.CYP가족1-3중편마P450적기인균존재다태성,특별시CYP2C9、CYP2C19、CYP2D6화CYP3A5.초과일반적림상약물시유다태성P450개도대사,CYP기인적다태성시조성약물반응개체차이적주요원인.근궤년,허다여P450매활성화CYP기인표체상관적등위기인이피감정,인차통과분형CYP기인적공능성혹표첨(Tag)적유전변이,취가이획득개체적대사표형,유조우의생급시조도정학적용약방안,유효지제고약물료효화강저독부작용,특별시나사치료지수착적약물.현연,료해CYP기인적유전변이대우림상약물치료화약물개발시필불가소적.기인심편기술구유고다중수평화고통량적특점,사동시분형대량CYP기인유전변이성위가능,시실현개성화의료적중요기술보장.연이,DNA제비제약료예측성CYP기인분형심편적발전,기재림상상적엄범응용상수시일.
The human cytochrome P450 (CYP) enzymes play critical roles in the metabolism of numerous exogenous and endogenous molecules. All genes encoding P450 in families 1-3 are polymorphic,particularly CYP2C9,CYP2C19,CYP2D6 and CYP3A5. Polymorphic P450s are involved in the metabolism of more than 50% of clinical drugs. Genetic variation in the CYP genes is he main cause for individual variation in drug response. Over the past several years,Alleles are responsible for the variable enzymatic activity of P450 and the variable expression of CYP genes,have been identified. The phenotype can be determined by genotyping the functional variants or tag variants of the CYP genes. This helps doctors to choose ppropriate medication for patients to enhance the curative effect and to reduce the side effect,especially when drugs with narrow therapeutic index are involved. Knowledge of genetic variants of the CYP genes is necessary for both drug therapy and drug development. With a high degree of multiplexing,microarrays offer promise for simultaneously enotyping a large number of genetic variants of CYP genes,and thus provide technical basis for realizing personalized medicine. However,DNA preparation is the bottleneck for developing microarrays for genotyping genetic variants of the CYP genes. Extensive application of predictive CYP microarrays in clinical practice will be made in the near uture.