Arrigoni Elena, Del Re Marzia, Fidilio Leonardo, Fogli Stefano, Danesi Romano, Di Paolo Antonello
Clinical Pharmacology and Pharmacogenetic Unit, Department of Clinical and Experimental Medicine, University of Pisa, Via Roma 55, 56126 Pisa, Italy.
Department of Pharmacy, University of Pisa, Via Bonanno Pisano 6, 56126 Pisa, Italy.
Int J Mol Sci. 2017 Jan 6;18(1):104. doi: 10.3390/ijms18010104.
In the era of precision medicine, more attention is paid to the search for predictive markers of treatment efficacy and tolerability. Statins are one of the classes of drugs that could benefit from this approach because of their wide use and their incidence of adverse events.
Literature from PubMed databases and bibliography from retrieved publications have been analyzed according to terms such as statins, pharmacogenetics, epigenetics, toxicity and drug-drug interaction, among others. The search was performed until 1 October 2016 for articles published in English language.
Several technical and methodological approaches have been adopted, including candidate gene and next generation sequencing (NGS) analyses, the latter being more robust and reliable. Among genes identified as possible predictive factors associated with statins toxicity, cytochrome P450 isoforms, transmembrane transporters and mitochondrial enzymes are the best characterized. Finally, the solute carrier organic anion transporter family member 1B1 () transporter seems to be the best target for future studies. Moreover, drug-drug interactions need to be considered for the best approach to personalized treatment.
Pharmacogenetics of statins includes several possible genes and their polymorphisms, but muscular toxicities seem better related to variant alleles. Their analysis in the general population of patients taking statins could improve treatment adherence and efficacy; however, the cost-efficacy ratio should be carefully evaluated.
在精准医学时代,人们更加关注寻找治疗效果和耐受性的预测标志物。他汀类药物是一类因广泛使用及其不良事件发生率而能从这种方法中获益的药物。
根据他汀类药物、药物遗传学、表观遗传学、毒性和药物相互作用等术语,对来自PubMed数据库的文献和检索到的出版物的参考文献进行了分析。检索截至2016年10月1日发表的英文文章。
已经采用了几种技术和方法,包括候选基因分析和下一代测序(NGS)分析,后者更为强大和可靠。在被确定为与他汀类药物毒性相关的可能预测因素的基因中,细胞色素P450同工酶、跨膜转运蛋白和线粒体酶是特征最明显的。最后,溶质载体有机阴离子转运蛋白家族成员1B1()转运蛋白似乎是未来研究的最佳靶点。此外,为了实现个性化治疗的最佳方法,需要考虑药物相互作用。
他汀类药物的药物遗传学包括几个可能的基因及其多态性,但肌肉毒性似乎与变异等位基因关系更密切。在服用他汀类药物的普通患者群体中对其进行分析可以提高治疗依从性和疗效;然而,成本效益比应仔细评估。