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

Summary 1. 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 C 1; C 2 , C 3 and C 4 , and they have been observed in all the sera or plasmas studied. Most of the serum cholinesterase activity present is attributable to C 4 . C 1( C 2 and C 3 are only minor components. In paper electrophoresis at pH 8·6, C 1 , C 2 , C 3 and C 4 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 C 1 < C 3 < C 4 . C 2 has a slightly greater mobility than C 1 , C 3 and C 4 in paper electrophoresis at pH 8·6. 2. In some individuals a further zone (C 5 ) with properties of serum cholinesterase is present in addition to zones C 1; C 2 , C 3 and C 4 . C 5 has a slightly lower mobility than C 4 both in paper and starch gel electrophoresis at pH 8·6. The separation of C 5 from C 4 is improved in starch gel electrophoresis at pH 6·0. 3. Of 248 unrelated British individuals studied, 13 5% were found to be C 5 +. Of 213 Tristan da Cunha islanders studied 36 17% were found to be C 5 +. The incidence of the C 5 + 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 C 5 + 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 C 5 + individuals did not differ significantly from the mean DN and FNs of C 5 − individuals with the ‘usual’ phenotype. 5. The mean level of serum cholinesterase in C 5 + individuals was about 30% higher than that of C 5 − individuals of the ‘usual’ phenotype. The difference was highly significant. This result suggests that the C 5 component may be an extra component with no direct homologue in C 6 −individuals. 6. Studies on sixty relatives of nine randomly selected C 5 + individuals from the British population showed a highly significant familial concentration of C 5 +. The pedigrees suggest that C 5 + individuals may be heterozygous for a gene determining the formation of the C 5 component. The distribution of the C s + 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 C 5 component, because occasional instances of C 5 + individuals both of whose parents were C 5 − were observed. There is, however, considerable variation among C 5 + individuals in the amount of the C 6 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