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. 1992 Oct;51(4):821–828.

Identification of two different point mutations associated with the fluoride-resistant phenotype for human butyrylcholinesterase.

C P Nogueira 1, C F Bartels 1, M C McGuire 1, S Adkins 1, T Lubrano 1, H M Rubinstein 1, H Lightstone 1, A F Van der Spek 1, O Lockridge 1, B N La Du 1
PMCID: PMC1682781  PMID: 1415224

Abstract

The fluoride variant of human butyrylcholinesterase owes its name to the observation that it is resistant to inhibition by 0.050 mM sodium fluoride in the in vitro assay. Individuals who are heterozygous for the fluoride and atypical alleles experience about 30 min of apnea, rather than the usual 3-5 min, after receiving succinyldicholine. Earlier we reported that the atypical variant has a nucleotide substitution which changes Asp 70 to Gly. In the present work we have identified two different point mutations associated with the fluoride-resistant phenotype. Fluoride-1 has a nucleotide substitution which changes Thr 243 to Met (ACG to ATG). Fluoride-2 has a substitution which changes Gly 390 to Val (GGT to GTT). These results were obtained by DNA sequence analysis of the butyrylcholinesterase gene after amplification by PCR. The subjects for these analyses were 4 patients and 21 family members.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Alcântara V. M., Chautard-Freire-Maia E. A., Culpi L. CHE1 UF serum cholinesterase phenotype in whites and non-whites from southern Brazil as determined by a new method. Hum Hered. 1991;41(2):103–106. doi: 10.1159/000153986. [DOI] [PubMed] [Google Scholar]
  2. Allderdice P. W., Gardner H. A., Galutira D., Lockridge O., LaDu B. N., McAlpine P. J. The cloned butyrylcholinesterase (BCHE) gene maps to a single chromosome site, 3q26. Genomics. 1991 Oct;11(2):452–454. doi: 10.1016/0888-7543(91)90154-7. [DOI] [PubMed] [Google Scholar]
  3. Arpagaus M., Kott M., Vatsis K. P., Bartels C. F., La Du B. N., Lockridge O. Structure of the gene for human butyrylcholinesterase. Evidence for a single copy. Biochemistry. 1990 Jan 9;29(1):124–131. doi: 10.1021/bi00453a015. [DOI] [PubMed] [Google Scholar]
  4. Bartels C. F., James K., La Du B. N. DNA mutations associated with the human butyrylcholinesterase J-variant. Am J Hum Genet. 1992 May;50(5):1104–1114. [PMC free article] [PubMed] [Google Scholar]
  5. Bartels C. F., Jensen F. S., Lockridge O., van der Spek A. F., Rubinstein H. M., Lubrano T., La Du B. N. DNA mutation associated with the human butyrylcholinesterase K-variant and its linkage to the atypical variant mutation and other polymorphic sites. Am J Hum Genet. 1992 May;50(5):1086–1103. [PMC free article] [PubMed] [Google Scholar]
  6. Bartels C. F., van der Spek A. F., La Du B. N. Two polymorphisms in the non-coding regions of the BCHE gene. Nucleic Acids Res. 1990 Oct 25;18(20):6171–6171. doi: 10.1093/nar/18.20.6171-a. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Cooper D. N., Youssoufian H. The CpG dinucleotide and human genetic disease. Hum Genet. 1988 Feb;78(2):151–155. doi: 10.1007/BF00278187. [DOI] [PubMed] [Google Scholar]
  8. Dietz A. A., Rubinstein H. M., Lubrano T., Hodges L. K. Improved method for the differentiation of cholinesterase variants. Am J Hum Genet. 1972 Jan;24(1):58–64. [PMC free article] [PubMed] [Google Scholar]
  9. Doctor B. P., Chapman T. C., Christner C. E., Deal C. D., De La Hoz D. M., Gentry M. K., Ogert R. A., Rush R. S., Smyth K. K., Wolfe A. D. Complete amino acid sequence of fetal bovine serum acetylcholinesterase and its comparison in various regions with other cholinesterases. FEBS Lett. 1990 Jun 18;266(1-2):123–127. doi: 10.1016/0014-5793(90)81522-p. [DOI] [PubMed] [Google Scholar]
  10. Evans R. T., Wardell J. On the identification and frequency of the J and K cholinesterase phenotypes in a Caucasian population. J Med Genet. 1984 Apr;21(2):99–102. doi: 10.1136/jmg.21.2.99. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Gaughan G., Park H., Priddle J., Craig I., Craig S. Refinement of the localization of human butyrylcholinesterase to chromosome 3q26.1-q26.2 using a PCR-derived probe. Genomics. 1991 Oct;11(2):455–458. doi: 10.1016/0888-7543(91)90155-8. [DOI] [PubMed] [Google Scholar]
  12. HARRIS H., WHITTAKER M. Differential inhibition of human serum cholinesterase with fluoride: recognition of two new phenotypes. Nature. 1961 Jul 29;191:496–498. doi: 10.1038/191496a0. [DOI] [PubMed] [Google Scholar]
  13. Hall L. M., Malcolm C. A. The acetylcholinesterase gene of Anopheles stephensi. Cell Mol Neurobiol. 1991 Feb;11(1):131–141. doi: 10.1007/BF00712805. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Hall L. M., Spierer P. The Ace locus of Drosophila melanogaster: structural gene for acetylcholinesterase with an unusual 5' leader. EMBO J. 1986 Nov;5(11):2949–2954. doi: 10.1002/j.1460-2075.1986.tb04591.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Jbilo O., Chatonnet A. Complete sequence of rabbit butyrylcholinesterase. Nucleic Acids Res. 1990 Jul 11;18(13):3990–3990. doi: 10.1093/nar/18.13.3990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. KALOW W., GENEST K. A method for the detection of atypical forms of human serum cholinesterase; determination of dibucaine numbers. Can J Biochem Physiol. 1957 Jun;35(6):339–346. doi: 10.1139/y57-041. [DOI] [PubMed] [Google Scholar]
  17. KALOW W., GUNN D. R. The relation between dose of succinylcholine and duration of apnea in man. J Pharmacol Exp Ther. 1957 Jun;120(2):203–214. [PubMed] [Google Scholar]
  18. KALOW W., LINDSAY H. A. A comparison of optical and manometric methods for the assay of human serum cholinesterase. Can J Biochem Physiol. 1955 Jul;33(4):568–574. [PubMed] [Google Scholar]
  19. LIDDELL J., LEHMANN H., DAVIES D. HARRIS AND WHITTAKER'S PSEUDOCHOLINESTERASE VARIANT WITH INCREASED RESISTANCE TO FLUORIDE. A STUDY OF FOUR FAMILIES AND THE IDENTIFICATION OF THE HOMOZGOTE. Acta Genet Stat Med. 1963;13:95–108. [PubMed] [Google Scholar]
  20. La Du B. N., Bartels C. F., Nogueira C. P., Arpagaus M., Lockridge O. Proposed nomenclature for human butyrylcholinesterase genetic variants identified by DNA sequencing. Cell Mol Neurobiol. 1991 Feb;11(1):79–89. doi: 10.1007/BF00712801. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Lockridge O., Bartels C. F., Vaughan T. A., Wong C. K., Norton S. E., Johnson L. L. Complete amino acid sequence of human serum cholinesterase. J Biol Chem. 1987 Jan 15;262(2):549–557. [PubMed] [Google Scholar]
  22. McGuire M. C., Nogueira C. P., Bartels C. F., Lightstone H., Hajra A., Van der Spek A. F., Lockridge O., La Du B. N. Identification of the structural mutation responsible for the dibucaine-resistant (atypical) variant form of human serum cholinesterase. Proc Natl Acad Sci U S A. 1989 Feb;86(3):953–957. doi: 10.1073/pnas.86.3.953. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. McTiernan C., Adkins S., Chatonnet A., Vaughan T. A., Bartels C. F., Kott M., Rosenberry T. L., La Du B. N., Lockridge O. Brain cDNA clone for human cholinesterase. Proc Natl Acad Sci U S A. 1987 Oct;84(19):6682–6686. doi: 10.1073/pnas.84.19.6682. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Muratani K., Hada T., Yamamoto Y., Kaneko T., Shigeto Y., Ohue T., Furuyama J., Higashino K. Inactivation of the cholinesterase gene by Alu insertion: possible mechanism for human gene transposition. Proc Natl Acad Sci U S A. 1991 Dec 15;88(24):11315–11319. doi: 10.1073/pnas.88.24.11315. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Nogueira C. P., McGuire M. C., Graeser C., Bartels C. F., Arpagaus M., Van der Spek A. F., Lightstone H., Lockridge O., La Du B. N. Identification of a frameshift mutation responsible for the silent phenotype of human serum cholinesterase, Gly 117 (GGT----GGAG). Am J Hum Genet. 1990 May;46(5):934–942. [PMC free article] [PubMed] [Google Scholar]
  26. Rachinsky T. L., Camp S., Li Y., Ekström T. J., Newton M., Taylor P. Molecular cloning of mouse acetylcholinesterase: tissue distribution of alternatively spliced mRNA species. Neuron. 1990 Sep;5(3):317–327. doi: 10.1016/0896-6273(90)90168-f. [DOI] [PubMed] [Google Scholar]
  27. Saiki R. K., Gelfand D. H., Stoffel S., Scharf S. J., Higuchi R., Horn G. T., Mullis K. B., Erlich H. A. Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase. Science. 1988 Jan 29;239(4839):487–491. doi: 10.1126/science.2448875. [DOI] [PubMed] [Google Scholar]
  28. Schumacher M., Camp S., Maulet Y., Newton M., MacPhee-Quigley K., Taylor S. S., Friedmann T., Taylor P. Primary structure of Torpedo californica acetylcholinesterase deduced from its cDNA sequence. 1986 Jan 30-Feb 5Nature. 319(6052):407–409. doi: 10.1038/319407a0. [DOI] [PubMed] [Google Scholar]
  29. Soreq H., Ben-Aziz R., Prody C. A., Seidman S., Gnatt A., Neville L., Lieman-Hurwitz J., Lev-Lehman E., Ginzberg D., Lipidot-Lifson Y. Molecular cloning and construction of the coding region for human acetylcholinesterase reveals a G + C-rich attenuating structure. Proc Natl Acad Sci U S A. 1990 Dec;87(24):9688–9692. doi: 10.1073/pnas.87.24.9688. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Sussman J. L., Harel M., Frolow F., Oefner C., Goldman A., Toker L., Silman I. Atomic structure of acetylcholinesterase from Torpedo californica: a prototypic acetylcholine-binding protein. Science. 1991 Aug 23;253(5022):872–879. doi: 10.1126/science.1678899. [DOI] [PubMed] [Google Scholar]
  31. Viby-Mogensen J., Hanel H. K. Prolonged apnoea after suxamethonium: an analysis of the first 225 cases reported to the Danish Cholinesterase Research Unit. Acta Anaesthesiol Scand. 1978;22(4):371–380. doi: 10.1111/j.1399-6576.1978.tb01313.x. [DOI] [PubMed] [Google Scholar]
  32. Viby-Mogensen J. Succinylcholine neuromuscular blockade in subjects heterozygous for abnormal plasma cholinesterase. Anesthesiology. 1981 Sep;55(3):231–235. doi: 10.1097/00000542-198109000-00008. [DOI] [PubMed] [Google Scholar]
  33. WHITTAKER M. THE PSEUDOCHOLINESTERASE VARIANTS: ESTERASE LEVELS AND INCREASED RESISTANCE TO FLUORIDE. Acta Genet Stat Med. 1964;14:281–285. doi: 10.1159/000151853. [DOI] [PubMed] [Google Scholar]

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