A second heterozygote for 'silent' and 'fluoride resistant' genes for serum cholinesterase.

Abstract

Genetically controlled variation is well established for cholinesterase in human serum, now known as acylcholine acylhydrolase (A.C.A.H., Enzyme Commission No. 3.1.1.8). Stimulus for investigation of variants of the enzyme arose from the observation that one genetic variant designated as atypical was responsible for prolonged apnoea following a standard dose of the muscle relaxant, succinylcholine (Kalow and Staron, 1957). Details of classification of phenotypes and genotypes for variants of cholinesterase and their relation to succinylcholine-sensitivity are summarized elsewhere (Motulsky, 1964; Lehmann and Liddell, 1964; Simpson and Kalow, 1966). The atypical variant of the enzyme is recognized by a low percentage inhibition of activity by dibucaine (known as dibucaine number or DN) when benzoylcholine is used as substrate compared to high inhibition for the usual type. The two forms of enzyme are controlled by two allelic genes known as Ela (for the atypical) and Elu (for the usual variant). Heterozygotes (ElUEla) are recognized by an intermediate DN. Subsequently, Liddell, Lehmann, and Silk (1962) and Hodgkin, Giblett, Levine, Bauer, and Motulsky (1965) described serum with no enzyme activity towards benzoylcholine, the gene for which the former authors named 'silent' (Els). Goedde, Gehring, and Hofmann (1965a, b), however, have evidence for minimal activity with benzoylcholine from sera from two subjects who were thought to be homozygous for the 'silent' gene. There is evidence for allelism of the Els gene with Ela and Elu genes (Simpson and Kalow, 1964). Differential inhibition by sodium fluoride combined with dibucaine inhibition has distinguished a third variant of the enzyme known as 'fluoride resistant' resulting from a gene known as Elf, with evidence that it is allelic to El and E., (Harris and