BUTYRYLCHOLINESTERASE GENES IN INDIVIDUALS WITH ABNORMAL INHIBITION NUMBERS AND WITH TRACE ACTIVITY - ONE COMMON MUTATION AND 2 NOVEL SILENT GENES

A random population was screened for abnormal dibucaine and fluoride n umbers (DN & FN) to find some common mutations in butyrylcholinesteras e (BCHE) gene. Of 2375 unrelated individuals, 10 were found to have lo w DN and FN and were selected for further studies. DNA analysis of the se hypocholinesterasemics revealed that seven patients were heterozygo us for missense mutation at codon 330 (TTA to ATA, BCHE330I). The fre quency of BCHE330I mutation was calculated to be at least 0.29% among the Japanese. On the other hand, two novel mutations were Found in th ree Families and two individuals including probands whose enzyme activ ity was very low (silent gene). Polymerase chain reaction and single s tranded conformation polymorphism (PCR-SSCP) and restriction fragment length polymorphism (PCR-RFLP) were used for identification of the com mon and known mutation types such as BCHE250P (ACT to CCT), BCHE*365R (GGA to CGA), and BCHE539T (GCA to ACA, K-polymorphism), whereas PCR -SSCP was used in combination with direct DNA sequencing for new mutat ions like BCHE446V (TTT to GTT) and BCHE*451X (GAA to TAA).