| Autor: |
Mikami, Liya R., Wieseler, Stacy, Souza, Ricardo L.R., Schopfer, Lawrence M., Nachon, Florian, Lockridge, Oksana, Chautard-Freire-Maia, Eleidi A. |
| Zdroj: |
Pharmacogenetics and Genomics; March 2008, Vol. 18 Issue: 3 p213-218, 6p |
| Abstrakt: |
Human butyrylcholinesterase (BChE; EC 3.1.1.8) is codified by the BCHEgene (3q26.1-q26.2) in which 65 variants have been identified. BChE is a scavenger of organophosphorus and carbamate compounds and hydrolyzes succinylcholine, mivacurium and cocaine. The present study describes 12 naturally occurring BCHEmutations including five new mutations (K12R, G15G, V294M, G333Cand R470W) identified in 366 blood donors from Southern Brazil. Exons 2 and 4 of the BCHEgene were examined by PCR-SSCA and samples with unexpected electrophoretic patterns were sequenced. The respective nucleotide substitution that characterizes each of the four new nonsynonymous mutations was introduced into BCHEcDNA by site directed mutagenesis and transfected into human embryonic kidney 293T cells andor Chinese hamster ovary cells. The catalyzed hydrolysis of butyrylthiocholine (BTC) by BChE was measured by the Ellman method. Enzyme kinetic parameters obtained after the expression of the respective recombinant BChE evaluated the effects of the four nonsynonymous mutations. Thirty-four out of 366 individuals carried a BChE mutation in exon 2. The Kvariant mutation, A539Tin exon 4, was present in one out of three persons. Gene expression showed that only one of the newly identified mutations (G333C) altered BChE activity, leading to a decrease of about 80 in relation to the wild-type enzyme. |
| Databáze: |
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