Frequency of butyrylcholinesterase gene mutations in individuals with abnormal inhibition numbers: an Italian-population study.
OBJECTIVE
More than 30 genetic variants of serum cholinesterase (butyrylcholinesterase, BChE) have been described. Some of them (the atypical and the fluoride-resistant variants) are well known because carriers are prone to develop prolonged apnea following the administration of the muscle relaxant succinylcholine. Genotype characterization is therefore important in order to prevent such episodes. Genetic studies have so far focused on selected individuals or families rather than on the random population.


METHODS
From a large group of healthy blood donors (n = 2609), we selected all the 58 individuals with low serum cholinesterase activity: among them 28 subjects had abnormal dibucaine and fluoride inhibition numbers. Twenty-five mutations in the coding region of the human cholinesterase gene were analyzed.


RESULTS
All individuals with abnormal inhibition numbers were homozygotes or double heterozygotes in several mutations. Asp70Gly (Atypical variant) and Ala539Thr (K variant) were the most frequently observed amino acid substitutions. The majority of subjects with low BChE activity but normal dibucaine and fluoride number presented only the K form. We analyzed 106 randomly chosen subjects for K and atypical variants. Carriers of these alleles were at risk of low BChE activity (OR = 9.55, 95%CI, 5.61-16.26 and OR = 30.33, 95%CI, 7.05-130.52 respectively).


CONCLUSIONS
Data obtained from this study help to better define the etiology of low BChE activity and the role of the rather common K allele. It is the first time that such a large population has been screened for so many mutations. BChE is also implicated in detoxifying cocaine; therefore genetic analysis could be useful in cases of cocaine toxicity in Italian subjects.
Lando
Giuliana
G
Laboratorio Analisi Chimico Cliniche Patologia Clinica, Ospedale Niguarda Ca' Granda, Milan, Italy.
Mosca
Andrea
A
Bonora
Roberto
R
Azzario
Franco
F
Penco
Silvana
S
Marocchi
Alessandro
A
Panteghini
Mauro
M
Patrosso
Maria Cristina
MC
D019943:Amino Acid Substitution; D001483:Base Sequence; D002091:Butyrylcholinesterase / Q000235:genetics*; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D017931:DNA Primers; D003992:Dibucaine / Q000494:pharmacology*; D005459:Fluorides / Q000494:pharmacology*; D005787:Gene Frequency; D014644:Genetic Variation / Q000235:genetics*; D005824:Genetics, Behavioral; D005838:Genotype; D006801:Humans; D007266:Inhibition, Psychological; D007558:Italy; D020125:Mutation, Missense
D002800:Cholinesterase Inhibitors; D017931:DNA Primers; D002091:Butyrylcholinesterase; D003992:Dibucaine; D005459:Fluorides