Bartels C F, James K, La Du B N
Department of Pharmacology, University of Michigan School of Medicine, Ann Arbor 48109-0572.
Am J Hum Genet. 1992 May;50(5):1104-14.
The J-variant of human serum butyrylcholinesterase (BChE) causes both an approximately two-thirds reduction of circulating enzyme molecules and a corresponding decrease in the level of BChE activity present in serum. Since the level of serum BChE activity and the duration of succinylcholine apnea are inversely correlated, this marked decrease in activity makes individuals with the J-variant more susceptible than usual subjects to prolonged apnea from succinylcholine. We reinvestigated the same family in which Garry et al. identified the J-variant phenotype. The atypical, fluoride, and K-variant mutations were also identified in members of the 47-person pedigree. DNA amplification by PCR, followed by direct sequencing of the amplified DNA, led to the finding that the J-variant phenotype of human serum BChE was associated with two DNA point mutations in the coding region. One of these was the mutation previously identified with the K-variant phenotype (GCA----ACA; Ala539----Thr). The other was an adenine-to-thymine transversion at nucleotide 1490, which changed amino acid 497 from glutamic acid to valine (GAA----GTA; Glu497----Val). This latter point mutation was named the J-variant mutation (formal name BCHE*497V). The J-variant mutation has not been identified without the K-variant mutation. The J-variant mutation created an RsaI-enzyme RFLP. Two additional point mutations, located in the noncoding regions of the gene, were also found to be linked with the J-variant and K-variant point mutations on the same allele. These noncoding polymorphic mutations had previously been found linked to the atypical and K-variant point mutations. A summary table shows dibucaine, fluoride, and Hoffmann-La Roche compound Ro 2-0683 inhibition numbers for 119 samples whose DNA has been sequenced. Eighteen BChE genotypes are represented.
人血清丁酰胆碱酯酶（BChE）的J变异型会使循环酶分子数量减少约三分之二，并相应降低血清中BChE活性水平。由于血清BChE活性水平与琥珀酰胆碱所致呼吸暂停的持续时间呈负相关，这种显著的活性降低使得携带J变异型的个体比正常受试者更容易因琥珀酰胆碱而出现长时间呼吸暂停。我们对Garry等人鉴定出J变异型表型的同一个家族进行了重新研究。在这个47人谱系的成员中还鉴定出了非典型、氟化物和K变异型突变。通过聚合酶链反应（PCR）进行DNA扩增，然后对扩增后的DNA进行直接测序，结果发现人血清BChE的J变异型表型与编码区的两个DNA点突变有关。其中一个是先前鉴定出与K变异型表型相关的突变（GCA----ACA；Ala539----Thr）。另一个是核苷酸1490处的腺嘌呤到胸腺嘧啶的颠换，它将氨基酸497从谷氨酸变为缬氨酸（GAA----GTA；Glu497----Val）。后一个点突变被命名为J变异型突变（正式名称为BCHE*497V）。未发现无K变异型突变的J变异型突变。J变异型突变产生了一种RsaI酶切限制性片段长度多态性（RFLP）。还发现另外两个位于基因非编码区的点突变与同一等位基因上的J变异型和K变异型点突变相关。这些非编码多态性突变先前已被发现与非典型和K变异型点突变相关。一个汇总表显示了119个已进行DNA测序样本的地布卡因、氟化物和霍夫曼 - 罗氏化合物Ro 2 - 0683抑制数值。代表了18种BChE基因型。
