Departments of Medical Genetics, Psychiatry, Physiology & Pharmacology, University of Calgary.
Alberta Children's Hospital Research Institute.
Curr Opin Psychiatry. 2019 Jan;32(1):7-15. doi: 10.1097/YCO.0000000000000465.
The implementation of pharmacogenetic testing in psychiatry is underway but is not yet standard protocol. Barriers to pharmacogenetics becoming standard practice are the lack of translation of evidence-based recommendations and standardization of genetic testing panels. As for the latter, there are currently no regulatory standards related to the gene and allele content of testing panels used to derive medication selection and dosing advice. To address these barriers, we summarize the current gene-drug interaction knowledgebase and proposed a minimum gene and allele set for pharmacogenetic testing in psychiatry.
The Pharmacogenomics Knowledgebase has cataloged 448 gene-drug interactions relevant to psychiatry based on the current scientific literature, drug labels, and pharmacogenetic-based implementation guidelines. A majority of these interactions involved two cytochrome P450 enzymes (CYP2D6 and CYP2C19) and antidepressant medications, however, CYP2C9, HLA-A, and HLA-B are relevant to mood stabilizers/anticonvulsants.
On the basis of evidence base, we proposed a minimum gene and allele set for pharmacogenetic testing in psychiatry that includes 16 variant alleles within five genes (CYP2C9, CYP2C19, CYP2D6, HLA-A, HLA-B). The intent is to assist clinicians in judging the gene and allele content of pharmacogenetic tests and to facilitate pharmacogenetic testing as a standard protocol and companion tool for psychotropic medication selection and dosing.
精神医学领域的药物遗传学检测已经在实施中,但尚未成为标准操作流程。药物遗传学检测难以成为标准操作流程的原因,在于缺乏对基于证据的推荐意见的转化以及遗传检测面板的标准化。就后者而言,目前用于推导药物选择和剂量建议的检测面板,在基因和等位基因内容方面尚无监管标准。为了解决这些障碍,我们总结了当前的基因-药物相互作用知识库,并提出了精神医学中药物遗传学检测的最小基因和等位基因集。
基于当前的科学文献、药物标签和基于药物遗传学的实施指南,药物遗传学知识库已经将 448 种与精神医学相关的基因-药物相互作用进行了分类。这些相互作用大多数涉及两种细胞色素 P450 酶(CYP2D6 和 CYP2C19)和抗抑郁药物,然而 CYP2C9、HLA-A 和 HLA-B 与心境稳定剂/抗惊厥药有关。
基于循证医学证据,我们提出了精神医学中药物遗传学检测的最小基因和等位基因集,包括五个基因(CYP2C9、CYP2C19、CYP2D6、HLA-A、HLA-B)中的 16 个变异等位基因。目的是帮助临床医生判断药物遗传学检测的基因和等位基因内容,并促进药物遗传学检测成为精神药物选择和剂量的标准操作流程和配套工具。