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实体器官移植药物遗传学中的新挑战与前景:免疫抑制药物药效学相关蛋白质的遗传变异性

New challenges and promises in solid organ transplantation pharmacogenetics: the genetic variability of proteins involved in the pharmacodynamics of immunosuppressive drugs.

作者信息

Pouché Lucie, Stojanova Jana, Marquet Pierre, Picard Nicolas

机构信息

Inserm, UMR 850, 2 Avenue Martin-Luther King, F-87042 Limoges, France.

CHU Limoges, Department of Pharmacology, Toxicology & Pharmacovigilance, 2 Avenue Martin-Luther King, F-87042 Limoges, France.

出版信息

Pharmacogenomics. 2016 Feb;17(3):277-96. doi: 10.2217/pgs.15.169. Epub 2016 Jan 22.

Abstract

Interindividual variability in immunosuppressive drug responses might be partly explained by genetic variants in proteins involved in the immune response or associated with IS pharmacodynamics. On a general basis, the pharmacogenetics of drug target proteins is less known and understood than that of proteins involved in drug disposition pathways. The aim of this review is to facilitate research related to the pharmacodynamics of the main immunosuppressive drugs used in solid organ transplantation. We elaborated a quality of evidence grading system based on a literature review and identified 'highly recommended', 'recommended' or 'potential' candidates for further research. It is likely that a number of additional rare variants might further explain drug response phenotypes in transplantation, and particularly the most severe ones. The advent of next-generation sequencing will help to identify those variants.

摘要

免疫抑制药物反应的个体间差异可能部分由免疫反应中涉及的蛋白质或与免疫抑制剂药效学相关的基因变异来解释。一般来说,药物靶蛋白的药物遗传学比参与药物处置途径的蛋白质的药物遗传学了解得更少。本综述的目的是促进与实体器官移植中使用的主要免疫抑制药物药效学相关的研究。我们在文献综述的基础上制定了证据质量分级系统,并确定了“强烈推荐”“推荐”或“有潜力”的进一步研究候选对象。很可能还有许多其他罕见变异可能进一步解释移植中的药物反应表型,尤其是最严重的表型。新一代测序技术的出现将有助于识别这些变异。

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