Haplotypes of butyrylcholinesterase K-variant and their influence on the enzyme activity.

Butyrylcholinesterase (BChE) is a serine hydrolase widely distributed throughout the body. It provides protection against administrated or inhaled poisons by hydrolyzing or sequestering the toxic compounds. The most frequent genetic variant of BCHE gene - K variant (p.A539T) is located in the C-terminal tetramerization domain, outside of the catalytic center. Many studies tried to reveal the nature of the lower activity of BChE K-variant but results and conclusions were often contradictory. The aim of this study is to estimate K allele frequency and its coexisting alterations in BCHE gene in a population of 162 individuals, as well as, assess influence on the enzyme activity in serum. We present three haplotypes of BChE-K variant, two of them coexist in strong linkage disequilibrium with alterations in 5'UTR (rs1126680), intron 2 (rs55781031) or in exon 2 (rs1799807). We demonstrate a negative role of these alterations on enzyme activity. By oneself BCHE-K (with no other alterations in BCHE gene) haplotype exhibits wild type enzyme activity. Based on our previous and presented results we conclude that SNPs localized outside the coding sequence, in 5'UTR or/and in intron 2 of BCHE gene, but not solely in K-variant alteration (p.A539T) itself, are responsible for reduced enzyme activity.

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