Concordance of Butyrylcholinesterase Phenotype With Genotype

Abstract

Butyrylcholinesterase (BChE) metabolizes the paralytic succinylcholine. Extended paralysis occurs in people with inherited BChE variants that may be identified by measuring BChE activity with and without the inhibitor dibucaine to calculate a dibucaine number (DN). Accurate phenotyping requires phenotype-specific BChE and DN reference intervals. We investigated the concordance between the biochemical BChE phenotype and the BCHE genotype to establish interpretive criteria for biochemical results. DNA was extracted from 45 serum specimens for which BChE activity and DN had been determined. The BCHE gene coding region was amplified and sequenced. Phenotype-genotype concordance and discordance occurred in 16 (36%) and 15 (33%) of specimens, respectively. A phenotype could not be assigned for 14 specimens (31%). An incorrectly assigned phenotype did not change the risk of prolonged paralysis or implied a slightly increased risk when there was none. Accurate BChE phenotyping is difficult using only enzyme activity and DN. The combination of biochemistry and BCHE genotype could improve the assessment of patient risk.

PharmGKB summary

“…The BCHE gene is located on chromosome 3q26.1-26.2 and is approximately 64 Kb long [14, 15]. Since the initial discovery of the A-variant of BCHE , over 60 polymorphisms in the BCHE gene have been reported [15].…”

“…Since the initial discovery of the A-variant of BCHE , over 60 polymorphisms in the BCHE gene have been reported [15]. Genetic variants that impair BCHE enzyme activity can be broadly classified as being either “qualitative” or “quantitative” variants.…”

“…The qualitative variants affect BCHE enzyme substrate affinity whereas the quantitative variants affect the quantity of enzyme that is produced without affecting BCHE substrate affinity. Both types of variants increase a patient's risk of prolonged apnea in the presence of SCH, but the duration of the apnea depends on the type and number of variants present [11, 15, 16]. A list of the most common genetic variants of BCHE can be found in Table 1.…”

Butyrylcholinesterase as a biochemical marker

“…In order to examine the form of BChE, an assay of either dibucaine number (commonly abbreviated as DN) or fl uoride number (commonly abbreviated as FN) is suitable for their distinguishing (53,54). The assay is based either on inhibition of BChE by dibucaine (cinchocaine) (Fig.…”

A Patient with Prolonged Paralysis

“…Failure to do so can produce misleading results or uninterpretable biochemical data that could lead to an error, for example, in which the phenotype obtained implies no or only a slight risk of prolonged paralysis in an individual who is actually at high risk. In one study (12 ), 3 patients were assigned a BChE phenotype of UF (slight risk), but 1 of the patients was determined to have an AA BCHE genotype (high risk) (12 ).…”