基于2014－2019年室間質評數據的我國臨床藥物基因組學發展現狀分析

陳幽攸 李華云 任小群 代顏

摘 要 目的：為推進臨床個體化用藥提供參考。方法：在國家衛生健康委臨床檢驗中心（NCCL）和國家藥品監督管理局（NMPA）官網上提取截至2019年12月31日的有關化學藥物用藥指導的基因檢測室間質量評價（EQA）項目及獲批試劑盒的相關信息，統計各項目參評實驗室數量;以參與度較高的華法林和氯吡格雷藥物代謝基因多態性檢測EQA項目為例，分析各參評實驗室所用方法和檢測試劑盒情況，以分析我國臨床藥物基因組學（PGx）的發展現狀。結果：NCCL開展的藥物基因檢測EQA項目從2014年的3項增至2019年的9項;參評實驗室總數2018年為926個，2019年為1 249個。華法林和氯吡格雷藥物代謝基因多態性檢測參評實驗室數分別由最初的57、124個增至300.5、374.5個，各實驗室使用較廣泛的方法均為熒光聚合酶鏈式反應（PCR）法和PCR-芯片雜交法;目前，上述兩個項目獲NMPA批準的試劑盒數量分別為7、15個，但仍有部分參評實驗室使用自配試劑。結論：我國臨床PGx處于起步階段，實驗室的參評意識逐年提高;使用方法以熒光PCR法為主，但仍普遍存在使用自配試劑的情況，相關審批、使用、監管的制度均有待進一步完善。

關鍵詞 臨床藥物基因組學;室間質量評價;個體化用藥;華法林;氯吡格雷;發展現狀

ABSTRACT? ?OBJECTIVE： To provide reference for promoting individualized medication in clinic. METHODS： Information on external quality assessment （EQA） projects and approved kits for the guidance of chemical drug use were collected from the websites of National Center for Clinical Laboratories （NCCL） and National Medical Products Administration （NMPA） as of December 31， 2019. The number of laboratories participating in each evaluation project was count. Taking EQA projects of clopidogrel and warfarin drug metabolism gene polymorphism detection as examples， who was with the highest participation rate， the methods and? reagent kits of each laboratory were analyzed so as to analyze the current status of the clinical pharmacogenomics （PGx） in China. RESULTS： The number of PGx genetic test EQA projects conducted by NCCL increased from 3 （2014） to 9 （2019）. The total number of participating laboratories was 926 in 2018， and 1 249 in 2019. The number of laboratories of warfarin and clopidogrel drug metabolism gene polymorphism detection increased from 57 to 300.5 for warfarin and from 124 to 374.5 for clopidogrel. The more widely used methods were fluorescent PCR and PCR-chip hybridization. The number of reagent kits currently approved by NMPA was 7 for warfarin and 15 for clopidogrel， respectively. But some of the laboratories participating in EQA used self-prepared reagents yet. CONCLUSIONS： The clinical PGx is in its infancy， and the awareness of laboratories about EQA is improving; the main method was fluorescence PCR， but the use of self-made reagents in laboratories is still common，? regulations concerning the approval， use and supervision still need to be further improved.

KEYWORDS? ?Clinical pharmacogenomics; External quality assessment; In vitro diagnostic reagents; Warfarin;Clopidogrel;Development status

藥物基因組學（Pharmacogenomics，PGx）主要研究藥物代謝酶、轉運體與作用靶點的基因多態性等內容，可從深層次解釋藥物療效與安全性的個體差異[1-2]。除PGx基礎研究外，目前的研究重點還包括將發現的基因突變合理地應用于臨床，以助力臨床個體化用藥[3]。……