Sadhasivam S, Chidambaran V, Zhang X, Meller J, Esslinger H, Zhang K, Martin L J, McAuliffe J
1] Department of Anesthesia, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA [2] Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
1] Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA [2] Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Pharmacogenomics J. 2015 Apr;15(2):119-26. doi: 10.1038/tpj.2014.56. Epub 2014 Oct 14.
Opioid-related respiratory depression (RD) is a serious clinical problem as it causes multiple deaths and anoxic brain injuries. Morphine is subject to efflux via P-glycoprotein transporter encoded by ABCB1, also known as MDR1. ABCB1 polymorphisms may affect blood-brain barrier transport of morphine and therefore individual response to its central analgesic and adverse effects. This study aimed to determine specific associations between common ABCB1 genetic variants and clinically important outcomes including RD and RD resulting in prolonged stay in hospital with intravenous morphine in a homogenous pediatric surgical pain population of 263 children undergoing tonsillectomy. Children with GG and GA genotypes of ABCB1 polymorphism rs9282564 had higher risks of RD resulting in prolonged hospital stays; adding one copy of the minor allele (G) increased the odds of prolonged hospital stay due to postoperative RD by 4.7-fold (95% confidence interval: 2.1-10.8, P=0.0002).
阿片类药物相关的呼吸抑制（RD）是一个严重的临床问题，因为它会导致多起死亡和缺氧性脑损伤。吗啡可通过由ABCB1（也称为MDR1）编码的P-糖蛋白转运体流出。ABCB1基因多态性可能会影响吗啡的血脑屏障转运，从而影响个体对其中枢镇痛作用和不良反应的反应。本研究旨在确定常见ABCB1基因变异与临床重要结局之间的具体关联，这些结局包括RD以及在263名接受扁桃体切除术的同质儿科手术疼痛人群中因静脉注射吗啡导致住院时间延长的RD。ABCB1基因多态性rs9282564的GG和GA基因型儿童发生RD导致住院时间延长的风险更高；每增加一个拷贝的次要等位基因（G），术后RD导致住院时间延长的几率增加4.7倍（95%置信区间：2.1-10.8，P=0.0002）。
