Cholinesterases genes

Soreq, H. and Zakut, H. (1990) Cholinesterase Genes Multileveled Regulation. Karger, Basel, 108 pp. 

K. Muratanai, T. Hada, Y. Yamamoto, T. Kaneko, Y. Shigeto, T. Ohue, J. Furuyama, K. Higashino, Inactivation of the Cholinesterase Gene by Alu Insertion Possible Mechanism for Human Gene Transposition , Proc. Natl. Acad. Sci. USA, 88,11315-11319 (1991). 

In other studies, two families segregating for a new cholinesterase gene designated El[ were discovered by Rubinstein et al. (R13). The presence of a new variant was deduced by the same methods that were used to characterize the E variant, and it was proposed that the variant produces the Ey enzyme, but that the serum level is reduced by about 33%. So far, only the EjE variant has been distinguishable by use of inhibitors. The criticisms applied to the E( variant apply to this variant as well. 

The discovery of an individual having no detectable serum cholinesterase activity was reported by Liddell et al. (L33) in 1962. Such individuals are said to possess a silent gene for cholinesterase, and to date, about 105 subjects have been reported to be homozygous for silent cholinesterase. Simpson and Kalow (S27) presented evidence that the silent cholinesterase gene is allelic to the usual cholinesterase gene. 

Statistical analysis of familial data by Scott (SI 3) led to the conclusion that the type I and type II silent cholinesterases (referred to by Scott as type O and type T, respectively) are allelic to one another and, by extension, to the Ey gene (S16). As indicated above, and in Section 2.7, some populations have an unexpectedly high incidence of a silent cholinesterase gene (A17, G33, PI, S17). 

G5. Garry, P. J., Atypical (Ef) and fluoride-resistant (E ) cholinesterase genes Absent in a native American Indian population. Hum Hered. 27, 433-436 (1977). 

Prody, C. A, Dreyfus, P., Zamir, R.. Zakut, H., and Soreq, H. (1989). Dc novo amplillcation within a silent human cholinesterase gene in a family subjected to proionged exposure to organophos-phorou.s Insecticides. Proc. Natl. Acad. Sci. USA 86,690-694. 

Damodaran, T.V., Jones, K.H., Patel, A.G., et al., 2003. Sarin (nerve agent GB)-induced differential expression of mRNA coding for the acetyl-cholinesterase gene in the rat central nervous system. Biochem. Pharmacol. 65, 2041-2047. 

Valle, A.M., Radic, Z., Rana, B.K., et al., 2011. Naturally occurring variations in the human cholinesterase genes heritability and association with cardiovascular and metabolic traits. J. Pharmacol. Exp. Ther. 338 (1), 125-133. 

Taylor, P. and Radic, Z. The cholinesterases from genes to proteins. Annu. Rev. Pharmacol. Toxicol. 34 281-320, 1994. 

Improvements in medication by use of acetyl cholinesterase inhibitors and general therapy significantly reduce symptoms at the onset of the disease [3, 4] but do not address the severe mortality in the final stages. A causal therapy is, therefore, still very much in demand, because no existing therapy effectively stops or even cures the disease. Identification of gene mutations linked to Alzheimer s disease-afflicted families in London and Sweden and additional polymorphisms that either cause or promote Alzheimer s disease have provided some insight into the biological pathways and the involvement of the amyloid precursor protein (APP) [5-8],... 

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