Max Planck Institute of Psychiatry, Munich, Germany.
Curr Pharm Des. 2011;17(26):2843-51. doi: 10.2174/138161211797440140.
Polymorphisms in the drug transporter gene ABCB1 account for differences in the clinically efficacy of the most drugs, most likely by influencing their access to the brain. The majority proportion of depressed patients, given a regular dose, do not respond properly or experience severe side effects. One explanation may be the polymorphisms in the drug transporter gene ABCB1, which account for differences in the clinical efficacy of antidepressants, neuroleptics or mood stabilizers most likely by influencing their access to the brain. If patients are treated with a substrate of P-gp, functionally relevant genetic variants in the ABCB1 transporter could influence intracerebral drug concentrations and, thereby, clinical response. The review shows recently investigated clinical impact of ABCB1 variants including the three most important SNPs rs1045642, rs2032582, and rs2032583. In the paper, with respect not to go beyond the scope of this review, we will focus on these three SNPs. The final goal of pharmacogenetics is to help clinicians to choose the best treatment for each individual patient. >From the evidence reviewed in this publication, it is likely that combination of metabolizing and drug target polymorphisms will produce the best prediction for the selection of the optimal dose and optimal drug as a function of the individual` s genetic profile.
ABCB1 药物转运体基因的多态性导致大多数药物的临床疗效存在差异，很可能是通过影响它们进入大脑的途径。大多数接受常规剂量治疗的抑郁症患者反应不佳或出现严重副作用。一种解释可能是 ABCB1 药物转运体基因的多态性，它很可能通过影响抗抑郁药、神经安定药或情绪稳定剂进入大脑的途径，导致这些药物的临床疗效存在差异。如果患者使用 P-糖蛋白的底物进行治疗，那么 ABCB1 转运体中的功能性相关遗传变异可能会影响颅内药物浓度，并因此影响临床反应。该综述显示了最近研究的 ABCB1 变异对临床的影响，包括三个最重要的 SNPs（rs1045642、rs2032582 和 rs2032583）。在本文中，鉴于不超出本综述的范围，我们将重点关注这三个 SNPs。药物遗传学的最终目标是帮助临床医生为每个个体患者选择最佳治疗方案。从本出版物中回顾的证据来看，代谢酶和药物靶点多态性的组合很可能会产生最佳预测，从而根据个体的遗传特征选择最佳剂量和最佳药物。
