Genetical studies on a new variant of serum cholinesterase detected by electrophoresis.

Abstract

Summary1. At least four distinct zones with properties of serum cholinesterase (pseudocholinesterase) may be demonstrated by starch gel electrophoresis of normal serum or plasma. These have been called C1; C2, C3 and C4, and they have been observed in all the sera or plasmas studied. Most of the serum cholinesterase activity present is attributable to C4. C1( C2 and C3 are only minor components. In paper electrophoresis at pH 8·6, C1, C2, C3 and C4 have essentially the same mobility. Since they are well separated at this pH in starch gel electrophoresis it seems likely that they may represent a series of polymers of increasing molecular weight C1 < C3 < C4. C2 has a slightly greater mobility than C1, C3 and C4 in paper electrophoresis at pH 8·6.2. In some individuals a further zone (C5) with properties of serum cholinesterase is present in addition to zones C1; C2, C3 and C4. C5 has a slightly lower mobility than C4 both in paper and starch gel electrophoresis at pH 8·6. The separation of C5 from C4 is improved in starch gel electrophoresis at pH 6·0.3. Of 248 unrelated British individuals studied, 13 5% were found to be C5+. Of 213 Tristan da Cunha islanders studied 36 17% were found to be C5+. The incidence of the C5+ phenotype did not vary significantly in different age groups, or between the two sexes.4. In the British population 96 % had the ‘usual’ serum cholinesterase phenotype as denned by dibucaine and fluoride number determination, and 4% had the ‘intermediate’ phenotype. All the C5+ individuals had the ‘usual’ phenotype. In the Tristan da Cunha islanders all individuals studied had the ‘usual’ phenotype. The mean DN and FNs for the C5+ individuals did not differ significantly from the mean DN and FNs of C5− individuals with the ‘usual’ phenotype.5. The mean level of serum cholinesterase in C5+ individuals was about 30% higher than that of C5− individuals of the ‘usual’ phenotype. The difference was highly significant. This result suggests that the C5 component may be an extra component with no direct homologue in C6−individuals.6. Studies on sixty relatives of nine randomly selected C5+ individuals from the British population showed a highly significant familial concentration of C5+. The pedigrees suggest that C5+ individuals may be heterozygous for a gene determining the formation of the C5 component. The distribution of the Cs+ phenotype in the complex pedigree of the Tristan da Cunha islanders was also found to be consistent with this hypothesis.If the hypothesis is correct then one must assume that not all presumptive heterozygotes exhibit the C5 component, because occasional instances of C5+ individuals both of whose parents were C5− were observed. There is, however, considerable variation among C5+ individuals in the amount of the C6 component present, and it is quite possible that the methods used here might have failed to detect the component if it were present only in very small amounts.We are grateful to the Medical Research Council Working Party on Tristan da Cunha for providing the blood specimens from the islanders.* We also wish to thank Miss Barbara Brown