ABSTRACT Introduction: Several reports suggest a possible association between polymorphisms in the cytochrome P450 2C9 (CYP2C9) gene and the risk for non-steroidal anti-inflammatory drug (NSAID)-related adverse gastrointestinal events, including gastrointestinal bleeding. Because findings were controversial, a systematic review and a meta-analysis of eligible studies on this putative association was conducted. Areas covered: The authors have revised the relationship between CYP2C9 polymorphisms and the risk of developing NSAID-related gastrointestinal bleeding, as well as other adverse gastrointestinal events, and performed meta-analyzes. The bias effect and potential sources of heterogeneity between studies was analyzed. Expert opinion: Individuals classified as poor metabolizers after CYP2C9 genotyping (activity scores equal to 0 or 0.5) have an increased risk of developing NSAID-related gastrointestinal adverse events with an odds ratio (OR) = 1.86, (p = 0.004) and the OR for subjects with gastrointestinal bleeding is = 1.90, (p = 0.003). Gene-dose effect for variant CYP2C9 alleles (p = 0.005 for all gastrointestinal adverse events, and p = 0.0001 for bleeding patients) was observed. Also, there is an allele-specific effect in the association: CYP2C9*2 is a poor risk predictor, whereas CYP2C9*3 is a highly significant predictor of gastrointestinal adverse events (p = 0.006) and gastrointestinal bleeding (p = 0.0007).

中文翻译：

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NSAID 代谢和胃肠道出血风险的药物基因组学更新

摘要 介绍：一些报告表明，细胞色素 P450 2C9 (CYP2C9) 基因的多态性与非甾体抗炎药 (NSAID) 相关的胃肠道不良事件（包括胃肠道出血）的风险之间可能存在关联。由于研究结果存在争议，因此对这种假定关联的合格研究进行了系统评价和荟萃分析。涵盖领域：作者修改了 CYP2C9 多态性与发生 NSAID 相关胃肠道出血以及其他胃肠道不良事件的风险之间的关系，并进行了荟萃分析。分析了研究之间的偏倚效应和异质性的潜在来源。专家意见：在 CYP2C9 基因分型后被归类为代谢不良的个体（活动评分等于 0 或 0。5) 发生 NSAID 相关胃肠道不良事件的风险增加，优势比 (OR) = 1.86 (p = 0.004)，胃肠道出血受试者的 OR = 1.90 (p = 0.003)。观察到变异 CYP2C9 等位基因的基因剂量效应（所有胃肠道不良事件 p = 0.005，出血患者 p = 0.0001）。此外，该关联中存在等位基因特异性效应：CYP2C9*2 是较差的风险预测因子，而 CYP2C9*3 是胃肠道不良事件 (p = 0.006) 和胃肠道出血 (p = 0.0007) 的高度显着预测因子。观察到所有胃肠道不良事件为 005，出血患者为 p = 0.0001）。此外，该关联中存在等位基因特异性效应：CYP2C9*2 是较差的风险预测因子，而 CYP2C9*3 是胃肠道不良事件 (p = 0.006) 和胃肠道出血 (p = 0.0007) 的高度显着预测因子。观察到所有胃肠道不良事件为 005，出血患者为 p = 0.0001）。此外，该关联中存在等位基因特异性效应：CYP2C9*2 是较差的风险预测因子，而 CYP2C9*3 是胃肠道不良事件 (p = 0.006) 和胃肠道出血 (p = 0.0007) 的高度显着预测因子。