Influence of CYP2C9 and VKORC1 on patient response to warfarin: a systematic review and meta-analysis.
Influence of CYP2C9 and VKORC1 on patient response to warfarin: a systematic review and meta-analysis.
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CYP2C9 和 VKORC1 对患者对华法林反应的影响：系统评价和荟萃分析。
DOI：
10.1371/journal.pone.0044064
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Williamson PR
中科院分区：
文献类型：
--
作者：
Jorgensen AL;FitzGerald RJ;Oyee J;Pirmohamed M;Williamson PR
华法林是一种高效的抗凝剂，但其有效性依赖于将INR维持在治疗范围内。由于个体间差异较大，因此很难找到正确的剂量。CYP 2C 9和VKORC 1这两个基因与这种变异性相关，导致华法林标签中的基因型指导剂量表。尽管如此，目前仍不清楚基因型信息应如何在实践中使用。由于患者种族、研究结果、研究设计和方法学的严格性存在显著差异，因此很难通过文献来确定基因型如何影响特定患者的华法林反应。我们的系统性综述是为了公平和准确地解释哪些变异影响哪些结果，哪些患者以及在多大程度上。采用了全面的检索策略，纳入了117项研究。主要结局为稳定剂量、至稳定剂量的时间和出血事件。采用Jorgensen和威廉姆森的标准评估方法学质量，并采用先进的方法在荟萃分析中合成数据。对于CYP 2C 9 *3和稳定剂量（突变型需要1.1（0.7-1.5）和2.3（1.6-3.0）mg/天），大多数种族组的合并效应估计值具有显著性。对于大多数种族，VKORC 1和稳定剂量的效应估计值也具有显著性，尽管亚洲人和非亚洲人之间的方向不同（亚洲人中突变类型需要增加0.8（0.4-1.3）和1.5（1.1-1.8）mg/天，非亚洲人中需要减少1.5（0.7-2.2）和3.1（2.7-3.6）mg/天）。由于数据报告不充分，几项研究被排除。评估研究质量突出了方法严谨性的显著差异。值得注意的是，有大量证据表明存在选择性报告、成果和分析方法。与华法林反应的遗传相关性在种族之间存在差异。为了在不同人群中实现无偏估计，必须保持高水平的方法学严谨性，研究应报告足够的数据，以便纳入荟萃分析。我们提出了最低报告要求，提出了方法指南，并提供了减少选择性报告风险的建议。
Warfarin is a highly effective anticoagulant however its effectiveness relies on maintaining INR in therapeutic range. Finding the correct dose is difficult due to large inter-individual variability. Two genes, CYP2C9 and VKORC1, have been associated with this variability, leading to genotype-guided dosing tables in warfarin labeling. Nonetheless, it remains unclear how genotypic information should be used in practice. Navigating the literature to determine how genotype will influence warfarin response in a particular patient is difficult, due to significant variation in patient ethnicity, outcomes investigated, study design, and methodological rigor. Our systematic review was conducted to enable fair and accurate interpretation of which variants affect which outcomes, in which patients, and to what extent. A comprehensive search strategy was applied and 117 studies included. Primary outcomes were stable dose, time to stable dose and bleeding events. Methodological quality was assessed using criteria of Jorgensen and Williamson and data synthesized in meta-analyses using advanced methods. Pooled effect estimates were significant in most ethnic groups for CYP2C9*3 and stable dose (mutant types requiring between 1.1(0.7–1.5) and 2.3 (1.6–3.0)mg/day). Effect estimates were also significant for VKORC1 and stable dose for most ethnicities, although direction differed between asians and non-asians (mutant types requiring between 0.8(0.4–1.3) and 1.5(1.1–1.8)mg/day more in asians and between 1.5(0.7–2.2) and 3.1(2.7–3.6)mg/day less in non-asians). Several studies were excluded due to inadequate data reporting. Assessing study quality highlighted significant variability in methodological rigor. Notably, there was significant evidence of selective reporting, of outcomes and analysis approaches. Genetic associations with warfarin response vary between ethnicities. In order to achieve unbiased estimates in different populations, a high level of methodological rigor must be maintained and studies should report sufficient data to enable inclusion in meta-analyses. We propose minimum reporting requirements, suggest methodological guidelines and provide recommendations for reducing the risk of selective reporting.
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DOI：
10.1016/0735-1097(91)90585-w
发表时间：
1991-08-01
影响因子：
24
作者：
CONNOLLY, SJ;LAUPACIS, A;JOYNER, C
通讯作者：
JOYNER, C
DOI：
10.1097/00008571-199512000-00008
发表时间：
1995-12-01
期刊：
PHARMACOGENETICS
影响因子：
--
作者：
Furuya, H;FernandezSalguero, P;Idle, JR
通讯作者：
Idle, JR
影响因子：
2.1
作者：
Borgiani, P.;Ciccacci, C.;Novelli, G.
通讯作者：
Novelli, G.
影响因子：
158.5
作者：
EZEKOWITZ, MD;BRIDGERS, SL;DEYKIN, D
通讯作者：
DEYKIN, D
影响因子：
7.5
作者：
Bertola, JP;Mazoyer, E;Mahé, I
通讯作者：
Mahé, I