Population Diversity of Point Mutations in the Human AChE and BCHE Genes Predicts Variable Responses to Anticholinesterase Drugs
On an experimental basis, patients with neurodegenerative diseases receive anti-cholinesterases (Iversen, 1993; Enz et al., 1993; Giacobini, 1993) to improve cognitive function (Alzheimer’s disease) or to reduce muscle spasms (Parkinson’s disease). These drugs are directed toward the nervous system acetyl- and butyrylcholinesterase (AChE, BuChE). However, the response of specific individuals to such drugs was found to be highly variable. Molecular genetics findings strongly suggest that this variability may be due to genomic diversity in the corresponding genes, primarily in the BuChE gene, BCHE.
KeywordsJewish Population Serum Cholinesterase Anticholinesterase Agent Somatic Hybrid Cell Panel Molecular Genetic Finding
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- Arbel, R. and Magal, L., 1992, “In the Land of the Golden Fleece, The Jews of Georgia and their Culture”, Ministry of Defense Publishing House, Tel-Aviv (in Hebrew).Google Scholar
- Ehrlich, G., Viegas-Pequignot, E., Ginzberg, D., Sindel, L., Soreq, H. and Zakut, H., 1992, Mapping the human acetylcholinesterase gene to chromosome 7q22 by fluorescent in situ hybridization coupled with selective PCR amplification from a somatic hybrid cell panel and chromosome-sorted DNA libraries, Genomics 13:1192–1197.PubMedCrossRefGoogle Scholar
- Ettinger, S., 1971, Georgia, in: “Encyclopaedia Judaica”, Keter Publishing House, Jerusalem, and sources quoted therein.Google Scholar
- Giacobini, E., 1993, Pharmacology of Alzheimer disease: new drugs and novel strategies, Prog. Brain Res. 98, 457–464.Google Scholar
- Iversen, L.L., 1993, Approaches to cholinergie therapy in Alzheimer’s disease, Prog. Brain Res. 98: 423426.Google Scholar
- Lev-Lehman, E., Ginzberg, D., Homreich, G., Ehrlich, G., Meshorer, A., Eckstein, F., Soreq H., and Zakut, H., Antisense inhibition of acetylcholinesterase gene expression causes transient hematopoietic alterations in vivo, Gene Therapy (in press).Google Scholar
- Lockridge, O., Bartels, C.F., Zelinski, T., Jbilo O., and Kris, M., 1992, Genetic variant of human acetylcholinesterase, in: ’Multidisciplinary Approaches to Cholinesterase Functions“, A. Shafferman and B. Velan, eds., Plenum Press, New York.Google Scholar
- McGuire, M.C., Nogueira, C.P., Bartels, C.F., Lightstone, H., Hajra, A., Van der Spek, A.F.L., Lockridge, O., and La Du BN, B.N., 1989, Identification of the structural mutation responsible for the dibucaine-resistant (atypical) variant form of human serum cholinesterase, Proc. Natl. Acad. Sci. U.S.A. 86: 953–957.Google Scholar
- Shoshani, T., Berkun, Y., Yahav, Y., Augarten, A., Bashan, N., Rivlin, Y., Gazit, E., Sereth, H., Kerem, E., and Kerem, B., 1993, A new mutation in the CFTR gene, composed of two adjacent DNA alterations, is a common cause of cystic fibrosis among Georgian Jews, Genomics 15: 236–237.PubMedCrossRefGoogle Scholar
- Soreq, H., and Zakut, H., 1993, “Human Cholinesterases and Anticholinesterases”, Academic Press, San Diego.Google Scholar
- Whittaker, M., 1986, “Cholinesterase”, Karger, Basel.Google Scholar