title: Naturally occurring mutation Leu307Pro of human butyrylcholinesterase in the Vysya community of India.
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.
authors.affiliation: Bharathiar University, Department of Biotechnology, Coimbatore, Tamil Nadu, India.
authors.forename: Indumathi
authors.initials: I
authors.lastname: Manoharan
authors.forename: Stacy
authors.initials: S
authors.lastname: Wieseler
authors.forename: Paul G
authors.initials: PG
authors.lastname: Layer
authors.forename: Oksana
authors.initials: O
authors.lastname: Lockridge
authors.forename: Rathnam
authors.initials: R
authors.lastname: Boopathy
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002091:Butyrylcholinesterase / Q000172:deficiency* / Q000235:genetics*; D002648:Child; D004252:DNA Mutational Analysis; D005091:Exons; D005260:Female; D006720:Homozygote; D006801:Humans; D007194:India; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D017354:Point Mutation
chemical_list: D002091:Butyrylcholinesterase