Preemptive Genotyping of CYP2C8 and CYP2C9 Allelic Variants Involved in NSAIDs Metabolism for Sickle Cell Disease Pain Management.
Preemptive Genotyping of CYP2C8 and CYP2C9 Allelic Variants Involved in NSAIDs Metabolism for Sickle Cell Disease Pain Management.
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参与镰状细胞病疼痛管理的非甾体抗炎药代谢的 CYP2C8 和 CYP2C9 等位基因变体的预先基因分型。
DOI：
10.1111/cts.12260
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发表时间：
2015
期刊：
影响因子：
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通讯作者：
Kutlar,Abdullah
中科院分区：
文献类型：
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作者：
Jaja,Cheedy;Bowman,Latanya;Wells,Leigh;Patel,Niren;Xu,Hongyan;Lyon,Matt;Kutlar,Abdullah
非甾体抗炎药治疗镰状细胞病（SCD）疼痛的镇痛作用的个体间差异归因于CYP 2C 8和CYP 2C 9酶的多态性。我们描述了一个非裔美国人SCD患者队列的CYP 2C 8和CYP 2C 9基因型/表型谱和急诊（艾德）就诊的频率。使用iPLEX ADME PGx多重检测板对165例无关患者的DNA进行了7种CYP 2C 8和15种CYP 2C 9等位基因的基因分型，确定了CYP 2C 8 *1（0.806）、*2（0.164）、*3（0.018）和 *4（0.012）等位基因。基因型频率分布为纯合子野生型（66.7%），杂合子（27.8%），纯合子变异/复合杂合子（5.4%）。CYP2C9 *1（0.824），*2（0.027），*3（0.012），*5（0.009），*6在预测的快代谢型（68.5%）、中等代谢型（18.1%）和弱代谢型（0.6%）中分别观察到 *（0.009）、*8（0.042）、*9（0.061）和 *11（0.015）。分别有52例和55例受试者至少有一个变异的CYP 2C 8或CYP 2C 9等位基因。虽然CYP 2C 9（p= 0.0515）表型在高和低艾德使用者中的分布略有显著性差异，但在15.2%（25）的队列中观察到一些CYP 2C 8和CYP 2C 9等位基因组合与较高的镇痛失败风险相关。CYP 2C 8和CYP 2C 9抢先基因分型可能使临床医生能够识别代谢表型受损的患者。
Interindividual variability in analgesic effects of nonsteroidal anti‐inflammatory drugs prescribed for sickle cell disease (SCD) pain is attributed to polymorphisms in theCYP2C8andCYP2C9enzymes. We describedCYP2C8andCYP2C9genotype/phenotype profiles and frequency of emergency department (ED) visits for pain management in an African American SCD patient cohort. DNA from 165 unrelated patients was genotyped for sevenCYP2C8and 15CYP2C9alleles using the iPLEX ADME PGx multiplexed panel.CYP2C8*1(0.806),*2(0.164), *3(0.018), and *4(0.012) alleles were identified. Genotype frequencies were distributed as homozygous wild type (66.7%), heterozygous (27.8%), and homozygous variant/compound heterozygous (5.4%), respectively.CYP2C9*1(0.824),*2(0.027),*3(0.012),*5(0.009),*6(0.009),*8(0.042), *9(0.061), and*11(0.015) were observed with extensive (68.5%), intermediate (18.1%) and poor predicted metabolizers (0.6%), respectively. Fifty‐two and 55 subjects, respectively had at least one variantCYP2C8orCYP2C9allele. Although the distribution of theCYP2C9(p= 0.0515) phenotypes was marginally significantly in high and low ED users; someCYP2C8andCYP2C9allelic combinations observed in 15.2% (25) of the cohort are associated with higher risks for analgesic failure.CYP2C8andCYP2C9preemptive genotyping could potentially enable clinicians to identify patients with impaired metabolic phenotypes.