Pharmacogenetics Guidelines: Overview and Comparison of the DPWG, CPIC, CPNDS, and RNPGx Guidelines.
Pharmacogenetics Guidelines: Overview and Comparison of the DPWG, CPIC, CPNDS, and RNPGx Guidelines.
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DOI：
10.3389/fphar.2020.595219
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发表时间：
2020
影响因子：
5.6
通讯作者：
Deneer VHM
中科院分区：
文献类型：
--
作者：
Abdullah-Koolmees H;van Keulen AM;Nijenhuis M;Deneer VHM
许多研究表明，药物治疗的疗效和副作用的风险受到遗传变异的影响。基于证据的指南对于在日常临床实践中实施药物遗传学知识以优化个体患者的药物治疗至关重要。进行了文献检索，以选定制定指导方针的委员会，并以英文出版建议。荷兰药物遗传学工作组（DPWG）、临床药物遗传学实施联盟（CPIC）、加拿大药物安全药物基因组学网络（CPNDS）和法国国家药物遗传学网络（RNPGx）入选。他们的指南在开发方法、基因型到预测表型的转化、药物治疗建议和基因分型建议方面进行了比较。详细概述了所有建议的基因药物组合给出。这些委员会有类似的指导方针制定方法。然而，在他们的项目开始时，目标不同，这导致了他们的指导方针的独特概况和优势。DPWG和CPIC主要关注结合患者基因型或预测表型的大量药物治疗建议。DPWG、CPNDS和RNPGx还建议在日常临床实践中进行基因检测，RNPGx甚至描述了推荐进行基因分型的特定临床环境或医疗条件。不协调是存在的，但是委员会也发起了协调项目。共识项目的结果是将“广泛代谢物（EM）”重新命名为“正常代谢物（NM）”。我们决定将一个CYP2D6基因型与一个无功能等位基因（活性评分1.0）翻译成中间代谢物（IM）的预测表型。建议的差异是所用方法的结果，例如评估三环类抗抑郁药的剂量调整。在某些情况下，会给出适应症或特定剂量的建议，例如氯吡格雷、可待因、伊立替康。建议基因检测最高水平的药物有：阿巴卡韦（HLA）、氯吡格雷（CYP2C19）、氟嘧啶（DPYD）、硫嘌呤（TPMT）、伊立替康（UGT1A1）、可待因（CYP2D6）、顺铂（TPMT）。该指南涵盖了许多药物和基因、基因型或预测表型。由于这一点及其独特的特点，考虑到指南的整体是有附加价值的。总之，许多有明确建议的基于证据的药物遗传学指南可供医疗保健专业人员、患者和其他利益相关者进行临床决策。
Many studies have shown that the efficacy and risk of side effects of drug treatment is influenced by genetic variants. Evidence based guidelines are essential for implementing pharmacogenetic knowledge in daily clinical practice to optimize pharmacotherapy of individual patients. A literature search was performed to select committees developing guidelines with recommendations being published in English. The Dutch Pharmacogenetics Working Group (DPWG), the Clinical Pharmacogenetics Implementation Consortium (CPIC), the Canadian Pharmacogenomics Network for Drug Safety (CPNDS), and the French National Network (Réseau) of Pharmacogenetics (RNPGx) were selected. Their guidelines were compared with regard to the methodology of development, translation of genotypes to predicted phenotypes, pharmacotherapeutic recommendations and recommendations on genotyping. A detailed overview of all recommendations for gene-drug combinations is given. The committees have similar methodologies of guideline development. However, the objectives differed at the start of their projects, which have led to unique profiles and strengths of their guidelines. DPWG and CPIC have a main focus on pharmacotherapeutic recommendations for a large number of drugs in combination with a patient’s genotype or predicted phenotype. DPWG, CPNDS and RNPGx also recommend on performing genetic testing in daily clinical practice, with RNPGx even describing specific clinical settings or medical conditions for which genotyping is recommended. Discordances exist, however committees also initiated harmonizing projects. The outcome of a consensus project was to rename “extensive metabolizer (EM)” to “normal metabolizer (NM)”. It was decided to translate a CYP2D6 genotype with one nonfunctional allele (activity score 1.0) into the predicted phenotype of intermediate metabolizer (IM). Differences in recommendations are the result of the methodologies used, such as assessment of dose adjustments of tricyclic antidepressants. In some cases, indication or dose specific recommendations are given for example for clopidogrel, codeine, irinotecan. The following drugs have recommendations on genetic testing with the highest level: abacavir (HLA), clopidogrel (CYP2C19), fluoropyrimidines (DPYD), thiopurines (TPMT), irinotecan (UGT1A1), codeine (CYP2D6), and cisplatin (TPMT). The guidelines cover many drugs and genes, genotypes, or predicted phenotypes. Because of this and their unique features, considering the totality of guidelines are of added value. In conclusion, many evidence based pharmacogenetics guidelines with clear recommendations are available for clinical decision making by healthcare professionals, patients and other stakeholders.
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影响因子：
6.7
作者：
Johnson JA;Caudle KE;Gong L;Whirl-Carrillo M;Stein CM;Scott SA;Lee MT;Gage BF;Kimmel SE;Perera MA;Anderson JL;Pirmohamed M;Klein TE;Limdi NA;Cavallari LH;Wadelius M
通讯作者：
Wadelius M
影响因子：
6.7
作者：
Goetz MP;Sangkuhl K;Guchelaar HJ;Schwab M;Province M;Whirl-Carrillo M;Symmans WF;McLeod HL;Ratain MJ;Zembutsu H;Gaedigk A;van Schaik RH;Ingle JN;Caudle KE;Klein TE
通讯作者：
Klein TE
影响因子：
6.7
作者：
Gonsalves, Stephen G.;Dirksen, Robert T.;Biesecker, Leslie G.
通讯作者：
Biesecker, Leslie G.
影响因子：
6.7
作者：
Crews, K. R.;Gaedigk, A.;Skaar, T. C.
通讯作者：
Skaar, T. C.
影响因子：
6.7
作者：
Brockmöller, J;Kirchheiner, J;Roots, I
通讯作者：
Roots, I