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Investigating naturally occurring variations in the Acetylcholinesterase gene of a human population
Author(s) -
Valle Anne Marie,
Radic Zoran,
Ho KwokYiu,
Mahboubi Vafa,
Wessel Jennifer,
Rao Fangwen,
Rana Brinda K.,
O’Connor Daniel T.,
Taylor Palmer
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1134.2
Subject(s) - acetylcholinesterase , single nucleotide polymorphism , biology , gene , population , genetics , genotype , cholinesterase , mutant , butyrylcholinesterase , aché , enzyme , biochemistry , pharmacology , medicine , environmental health
We are studying single nucleotide polymorphisms (SNPs) in the acetylcholinesterase (AChE ) gene of a human population in relation to catalytic properties and cardiovascular (CV) function. Cholinergic proteins play an important regulatory role in homeostatic maintenance of CV function. AChE found in whole blood enabled a biochemical characterization in addition to correlating genotype with phenotypic physiologic responses. Enzymatic activity determined in whole blood from twin and general population subject registries revealed significant relationships between AChE activity and certain CV endpoints. Also, the analysis enabled us to ascertain the impact of genetic variation and environmental influences on AChE activity. To date, we identified 19 SNPs of which 4 are non‐synonymous coding SNPs (cSNPs). Mutagenesis was conducted to introduce the non‐synonymous cSNPs into a human AChE cDNA vector with subsequent transfection into HEK cells for protein expression. Ongoing characterization of the purified mutant enzymes revealed significant thermal stability differences when compared with the predominant AChE species. With the structure of cholinesterase enzyme proteins and genes delineated, this research is relevant particularly in CV diseases and individual risks associated with chemical agent exposure affecting cholinergic function. Supported by NIH R37‐GM18360