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首页> 外文期刊>Pharmacogenomics >OCT1 genetic variants are associated with postoperative morphine-related adverse effects in children
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OCT1 genetic variants are associated with postoperative morphine-related adverse effects in children

机译：OCT1遗传变异与术后与儿童相关的吗啡相关的不良影响有关

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Aim: Large interindividual variability in morphine pharmacokinetics (PK) could contribute to variability in morphine analgesia and adverse events. Respiratory depression (RD) and postoperative nausea and vomiting (PONV) are significant adverse drug response of intravenous morphine in the perioperative setting limiting its efficacy in achieving adequate surgical pain relief. OCT1 is a transporter in the liver that transports morphine from the bloodstream into hepatocytes. Earlier we reported association of genetic polymorphisms in OCT1 with morphine PK, and lower morphine clearance in Caucasian children as compared with African-American (AA) children. The aim of this study is to identify the association between common OCT1 genotypes affecting morphine's PK and clinically important postoperative morphine-related adverse outcomes. Methods: After obtaining institutional review board (IRB) approval and informed consents, 311 children ages 6-15 years, American Society of Anesthesiologists' physical status 1 or 2 scheduled for tonsillectomy who received standard anesthetic, surgical and postoperative care were recruited. Clinical data collected included postoperative pain scores, total opioid use, incidence of PONV and RD. Four nonsynonymous SNPs of the OCT1 gene (rs12208357, rs34130495, rs72552763 and rs34059508) in each patient were genotyped using commercially available TaqMan assays. We investigated the genetic association of OCT1 with incidences of postoperative RD and PONV. Results: Caucasian and AA children differed significantly in the incidence of obstructive sleep apnea (p < 0.001) and total morphine use (p = 0.028). There were incidences of prolonged post anesthesia care unit stay in 7% of Caucasian children, while no such incidences were observed for AA children (p = 0.05). OCT1 polymorphism rs12208357 was associated with high incidences of PONV and PONV leading to prolonged post anesthesia care unit stay (p < 0.05). A significant association was also found between rs72552763 GAT deletion and high incidence of RD (p = 0.007). Conclusion: Children with certain OCT1 genotypes are associated with higher risk for RD and PONV following morphine administration leading to prolonged hospital stay. The OCT1 transporters' effects on morphine's PK could explain this association.
机译：目的：吗啡药代动力学（PK）中的大型细分变异性可能导致吗啡镇痛和不良事件的可变性。呼吸抑郁症（RD）和术后恶心和呕吐（PONV）是静脉内吗啡在围手术期静脉内静脉内静脉化的显着不良药物反应，限制其在实现足够的外科疼痛缓解中的功效。 Oct1是肝脏中的转运蛋白，将吗啡从血液中转化为肝细胞。早些时候，我们报道了10月份遗传多态性与吗啡PK的遗传多态性，以及白种人儿童的较低吗啡清除，与非洲裔美国人（AA）儿童相比。本研究的目的是鉴定影响吗啡PK的常见OCT1基因型之间的关联，临床上重要的术后吗啡相关的不良结果。方法：获得机构审查委员会（IRB）批准和知情同意，311岁以下儿童6-15岁，美国麻醉学家的身体状况1或2招募了接受标准麻醉，外科和术后护理的扁桃体切除术。收集的临床数据包括术后疼痛评分，总阿片类药物使用，PONV和RD的发病率。在每只患者的OCT1基因（RS12208357，RS34130495，RS32552763和RS72552763和RS34059508）中的四个无纯SNP是使用市售的Taqman测定的基因分型。我们调查了Oct1的遗传学协会，术后RD和PONV的发生率。结果：白种人和AA儿童在阻塞性睡眠呼吸暂停（P <0.001）的发生率和总体含量（P = 0.028）中有显着不同（P = 0.028）。延长后麻醉后护理单位的发生率在7％的白种人儿童中，而AA儿童没有观察到这样的发夹（P = 0.05）。 OCT1多态性RS12208357与PONV和PONV的高发血有关，导致麻醉后麻醉护理单元停留（P <0.05）。在Rs72552763 Gat缺失和Rd发病率高之间也发现了一个重要的关联（p = 0.007）。结论：某些OCT1基因型的儿童与Myphine行政管理到长期住院停留后RD和PONV的风险较高。 Oct1 Transporters对Myphine PK的影响可以解释这一协会。

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