琥珀酰胆碱或米库氯铵作用时间延长的患者，其丁酰胆碱酯酶基因存在新的突变。
Patients with prolonged effect of succinylcholine or mivacurium had novel mutations in the butyrylcholinesterase gene.
作者信息
Wichmann Sine, Færk Gitte, Bundgaard Jens R, Gätke Mona R
机构信息
aDanish Cholinesterase Research Unit, Department of Anaesthesiology, Herlev and Gentofte Hospital, University of Copenhagen bDepartment of Clinical Biochemistry, Herlev and Gentofte Hospital, Herlev cDepartment of Clinical Biochemistry, University of Copenhagen, Copenhagen, Denmark.
出版信息
Pharmacogenet Genomics. 2016 Jul;26(7):351-6. doi: 10.1097/FPC.0000000000000221.
INTRODUCTION
Mutations in the butyrylcholinesterase enzyme (BChE) can result in prolonged duration of action of the neuromuscular blocking agents, succinylcholine and mivacurium, as BChE hydrolyses these drugs. Hereditary low BChE activity can cause extensively prolonged apnoea during general anaesthesia when these drugs are used. The aim of this study was to describe novel mutations in the butyrylcholinesterase gene (BCHE) in patients who have experienced prolonged duration of action of mivacurium or succinylcholine.
METHODS
The Danish Cholinesterase Research Unit registers patients with prolonged duration of action to succinylcholine and mivacurium. Patients were studied if they had equivocal phenotypes on the basis of BChE activity, biochemical inhibitor reactions and with pedigree if possible. Complete nucleotide sequencing was performed to describe the genotype and pedigree was used to separate the alleles. Multiple sequence alignment of BChE was performed for comparison with other species.
RESULTS
Genotyping indicated seven novel mutations in the BCHE (I373T, G467S, W518R, L184S, V421A, M462I and R577H).
CONCLUSION
We have found seven new variants of the BCHE, which seem to reduce the activity of BChE in patients undergoing anaesthesia involving succinylcholine or mivacurium.
引言
丁酰胆碱酯酶（BChE）基因突变可导致神经肌肉阻滞剂琥珀酰胆碱和米库氯铵的作用时间延长，因为BChE可水解这些药物。遗传性低BChE活性在使用这些药物进行全身麻醉时可导致呼吸暂停时间大幅延长。本研究的目的是描述在米库氯铵或琥珀酰胆碱作用时间延长的患者中丁酰胆碱酯酶基因（BCHE）的新突变。
方法
丹麦胆碱酯酶研究单位登记琥珀酰胆碱和米库氯铵作用时间延长的患者。如果患者基于BChE活性、生化抑制剂反应以及可能的家系具有不明确的表型，则对其进行研究。进行完整的核苷酸测序以描述基因型，并使用家系来分离等位基因。对BChE进行多序列比对以与其他物种进行比较。
结果
基因分型表明BCHE中有七个新突变（I373T、G467S、W518R、L184S、V421A、M462I和R577H）。
结论
我们发现了BCHE的七个新变体，它们似乎降低了接受涉及琥珀酰胆碱或米库氯铵麻醉的患者的BChE活性。
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