E1k, another quantitative variant at cholinesterase locus 1.

Two families segregating for the atypical (E1a) allele at cholinesterase locus 1 are described. Unusual results for dibucaine inhibition led to the recognition of a new allele (E1k) also segregating in these families. The enzymatic and immunological data are consistent with the hypothesis that E1k causes reduction of 'usual' (E1u) molecules by about 33%. Whether the reduction of E1u caused by E1k is caused by retarded synthesis or accelerated degradation of serum cholinesterase remains to be determined.

Several quantitative variants at serum cholinesterase (E.C.3.1.1.8) locus 1 have been described. These result in lowered serum cholinesterase activity and, when interacting with the E,a (atypical) allele, give dibucaine inhibitions below those of E,UE,a heterozygotes.
Interaction with E,a led to the discovery of the E,s (Liddell et al., 1962) and Eli  variants. E,s exists in several forms (Rubinstein et al., 1970) and results in 95 to 100% diminution of E u molecules; E,J results in about 66% reduction. One family has been described in which several members have greatly increased amounts of apparently normal serum cholinesterase (Neitlich, 1966;Yoshida and Motulsky, 1969). The gene responsible has been named E Cynthiana but it is not yet known if it is active at cholinesterase locus 1 or locus 2.
We present here two families with a quantitative variant at cholinesterase locus 1 which results in about 33% reduction of E,u molecules; both of these families were recognised by means of interaction with the E, a gene.

Methods
The enzymatic and immunological methods used were the same as given in earlier publications Rubinstein et al., 1976;Dietz et al., 1973). (Table II in Garry et al. (1976) gives the cholinesterase activities and inhibitions of the known phenotypes as determined in our laboratory.) Received for publication 30 May 1977 Results S. FAMILY The index case (11.1) was discovered by means of prolonged apnoea after administration of succinylcholine. The cholinesterase activities and inhibitions of the sera of the family members are giveni in the Table. Two individuals (III.2 and 11I.3) have dibucaine inhibitions in a range not previously found. This family can be explained by assuming segregation for a new allele' which must have entered the family through 11.2 who is considered to be genotype E,uE, .
'Termed E,k in honour of Dr Werner Kalow who clarified the recognition and inheritance of the El' allele by means of dibucaine inhibition. The index case (11.2) was also discovered by prolonged apnoea after succinylcholine. The data on family members are given in the  Following the reasoning used for Eli , the Elk allele can be explained as resulting in reduced numbers of circulating E,u molecules whether because of reduced synthesis or accelerated degradation. Fig. 4 (derived from Fig. 4 of Garry et al., 1976) relates dibucaine inhibitions to mixtures of E,u and E a molecules in various proportions. The average dibucaine inhibition of the four E aE k subjects from the two families given above indicates that the ratio of E u to E,a molecules in their sera is about 40:60. This corresponds to an approximate 33% reduction of E1u molecules caused by the Elk allele. E,k causes less reduction of E1u molecules than Eli-33% vs 66%.
The average cholinesterase activity of EIaE1k sera should, therefore, be higher than that of ElaElJ sera. This is what is observed, 2.78 vs 1.93.
The relative diminution of E1u molecules in the sera of the two E aE k subjects (I1.1 and 111.2) in the J. family was also shown immunologically. cholinesterase activity of sera of various genotypes to immunological reactivity by gel immunodiffusion. The two E aE,k sera are found in an area of the plot distinct from EuE1U, EUE,a, and E aE a sera and close to that of E aE,J sera.

Discussion
The recognition of E,k in the two pedigrees given here is based on interaction of E1a with the resultant production of dibucaine inhibitions unlike any found hitherto-precisely the way in which Eli was also found . Inspection of Fig. 3 and 4 shows that other quantitative variants may well be discovered in the same way. Dibucaine inhibitions falling between 30 to 50%, if segregating appropriately, would indicate quantitative variants intermediate in their effects between E,s and E,3. Such variants, if they exist, should account for roughly 75 to 90% reduction of E u molecules.