Frequency of Atypical Pseudocholinesterase in British and Mediterranean Populations

Abstract

CONSIDEBABLE interest has been taken over the past twenty years in the level of human serum pseudo-cholinesterase, because it was known that it was altered ina number of pathological conditions. It has been recognized, however, in the past ten years that considerable differences may also exist in healthy people, and that this difference is genetically determined¹. Several variants of the enzyme are now known^2–5, but the variants which give rise to the most frequently found phenotypes are the ‘typical’ and ‘atypical’ enzyme of Kalow and Genest². These can be distinguished by their sensitivity to the pseudocholinesterase inhibitor dibucaine. Under given conditions the ‘typical’ enzyme is inhibited by about 80 per cent (‘Dibucaine Number’ or DN = 80), and the ‘atypical’ enzyme by about 20 per cent (DN = 20). The three phenotypes, ‘typical’ homozygotes, ‘atypical’ homozygotes and heterozygotes show a DN of about 80, 20 and 60 respectively. Kalow and Gunn⁶ found the gene frequency of the ‘atypical’ gene to be 0.0188 in a healthy Canadian population. ‘Atypical’ homozygotes would therefore be expected at a frequency of 1 in 3,000. This is of practical importance because they respond to the usually short acting, and in modern anaesthetics widely used muscle relaxant suxamethonium with a prolonged and dangerous apnœa, the normally short action of the drug being due to its rapid destruction by the ’typical‘ serum pseudocholinesterase. We had the impression that this anaesthetic hazard was more often encountered in persons of Mediterranean origin than in British patients. We have, therefore, determined the gene frequency of the ‘atypical’ gene in British and various Mediterranean populations by measuring the DN. The results are shown in Table 1. It may be noted that only heterozygotes and no ‘atypical’ homozygotes were discovered.