Naturally occurring mutation Leu307Pro of human butyrylcholinesterase in the Vysya community of India

Indumathi Manoharan, Stacy Wieseler, Paul G. Layer, Oksana Lockridge, Rathnam Boopathy

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

Abstract

BACKGROUND: People with genetic variants of butyrylcholinesterase (EC 3.1.1.8, BChE) can have hours of prolonged apnea after a normal dose of succinylcholine or mivacurium. METHODS: Plasma samples from 226 people in the Vysya community in Coimbatore, India were tested for BChE activity. RESULTS: Nine unrelated individuals had no detectable activity. DNA sequencing revealed a novel mutation in exon 2 of the BCHE gene, responsible for the silent phenotype of human serum BChE. All silent BChE samples were homozygous for a point mutation at codon 307 (CTT→CCT), resulting in substitution of leucine 307 by proline. Western blot analysis with a monoclonal antibody showed no BChE protein in plasma. Silent BChE plasma samples had no organophosphate-reactive BChE, as measured with FP-biotin. Expression of recombinant Leu307Pro BChE in cell culture confirmed that this mutant is expressed at very low levels. The proline substitution most likely destabilizes the BChE structure and causes the protein to be misfolded and rapidly degraded. CONCLUSIONS: This is the first report of a molecularly defined BChE mutation in the Indian population. The frequency of homozygous silent BChE in the Vysya community is 1 in 24, a value 4000-fold higher than the frequency of homozygous silent BChE in European and American populations.

Original languageEnglish (US)
Pages (from-to)461-468
Number of pages8
JournalPharmacogenetics and Genomics
Volume16
Issue number7
DOIs
StatePublished - Jul 2006

Keywords

  • Apnea
  • Butyrylcholinesterase
  • FP-biotin
  • Mivacurium
  • Silent variant
  • Succinylcholine

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Genetics(clinical)

Fingerprint Dive into the research topics of 'Naturally occurring mutation Leu307Pro of human butyrylcholinesterase in the Vysya community of India'. Together they form a unique fingerprint.

Cite this