Pseudocholinesterase variation.
Pseudocholinesterase variation.
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假胆碱酯酶变异。
DOI：
10.1007/978-3-642-67179-1_7
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发表时间：
1978
期刊：
影响因子：
--
通讯作者：
D. Agarwal
中科院分区：
文献类型：
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作者：
H. Goedde;D. Agarwal
由于其底物琥珀酰二胆碱是一种常用的短效肌肉松弛剂，因此血清胆碱酯酶基因决定的多态性具有特殊的意义。Lehmann和Ryan（1956年）、Kalow和Genest（1957年）以及Goedde等人（1964年）首次发现了不能水解药物的遗传变异。只有约三分之二的琥珀酰二胆碱敏感患者的所谓非典型等位基因纯合子可以很容易地识别与二布卡因抑制反应。其他变异是由于所谓的抗氟等位基因（Harris and Whittaker, 1961）和沉默等位基因——后者的特征是酶活性非常低（Liddell and Lehmann, 1963）或缺乏胆碱酯酶蛋白（Goedde et aI）。, 1965;Goedde和Altland， 1971)。虽然大多数具有非典型变异的个体在应用琥珀酰二胆碱后易出现延长的呼吸暂停，但并非所有临床实践中遇到的呼吸暂停病例都表现出血清酶的变异性质。据观察，超过30%的患有长时间呼吸暂停的患者不具有基因决定的胆碱酯酶变体。在这些病例中，酶在标准测定中似乎是正常类型，但显然不能在手术中水解药理学浓度的琥珀酰二胆碱。其他迄今为止未知的胆碱酯酶结构突变、药物相互作用或未被发现的肝脏疾病的存在已被讨论为这种差异的可能原因。几年前，我们与Behring公司合作开发了一种纯化的伪胆碱酯酶制剂（Goedde et aI）。, 1967)。对于由这种遗传缺陷引起的呼吸暂停延长的患者，可以通过注射这种制剂来完成酶替代，目前在德国医院普遍使用（Goedde和Altland， 1971）。在这篇论文中，我们报道了只对琥珀酰二胆碱敏感的新的胆碱酯酶变异的发生。家庭研究支持我们的发现。在232例使用琥珀酰二胆碱后呼吸暂停延长的患者中，我们将他们的血清发送给我们进行表型分析，我们只能将约7Q%的患者分类为已知的遗传变异（表1）。Kalow（1966）和Thompson and Whittaker（1966）在这类患者中观察到约40%的表型正常。在另一份报告中，Whittaker（1968）可以根据所谓的氯数解释两例具有正常表型的呼吸暂停病例。
The genetically determined polymorphism of serum cholinesterase is of special interest because its substrate succinyldicholine is a drug commonly used as a short-acting muscle relaxant. Genetic variants that failed to hydrolyze the drug were detected fo'r the first time by Lehmann and Ryan (1956), by Kalow and Genest (1957), and by Goedde et al.(1964). Only about two-thirds of the succinyldicholine-sensitive patients homozygous for the so-called atypical allele could be easily identified by inhibition reaction with dibucaine. Other variants are due to the so-called fluoride-resistant allele (Harris and Whittaker, 1961) and the silent allele-the latter characterized by very low enzyme activity (Liddell and Lehmann, 1963) or by the absence of cholinesterase protein (Goedde et aI., 1965; Goedde and Altland, 1971).Although most of the individuals who have an atypical variant are predisposed to prolonged apnea after application of succinyldicholine, not all of the apnea cases encountered in clinical practice always show a variant nature of the serum enzyme. It has been observed that more than 30% of the patients who suffered a prolonged apnea did not possess a genetically determined variant of cholinesterase. In these cases the enzyme appears to be a normal type in standard assays, but apparently does not hydrolyze succinyldicholine at pharmacologic concentrations during surgery. The presence of other hitherto unknown structural mutants of cholinesterase, drug interactions, or undetected liver disease have been discussed as possible reasons for this discrepancy. Some years ago, in cooperation with the Behring Company, we developed a purified pseudocholinesterase preparation (Goedde et aI., 1967). In patients with prolonged apnea caused by this genetic defect, enzyme replacement can be accomplished by injection of this preparation, which is nowadays commonly used in German hospitals (Goedde and Altland, 1971). In this paper, we report the occurrence of new cholinesterase variants sensitive only to succinyldicholine. Family studies support our findings. Out of 232 patients who had prolonged apnea after succinyldicholine, the sera of whom had been sent to us for phenotyping, we could classify only about 7Q% as having known genetic variants (Table 1). Kalow (1966) and Thompson and Whittaker (1966) observed about 40% normal phenotypes in such patients. In another report, Whittaker (1968) could explain two cases of apnea having a normal phenotype, on the basis of the so-called chloride number.