ORIGINAL ARTICLESNaturally occurring mutation Leu307Pro of human butyrylcholinesterase in the Vysya community of IndiaManoharan, Indumathia; Wieseler, Stacyb; Layer, Paul G.c; Lockridge, Oksanab; Boopathy, RathnamaAuthor Information aBharathiar University, Department of Biotechnology, Coimbatore, Tamil Nadu, India bUniversity of Nebraska Medical Center, Eppley Institute, Omaha, NE, USA cDarmstadt University of Technology, Developmental Biology & Neurogenetics, Darmstadt, Germany Correspondence and requests for reprints to Dr. Rathnam Boopathy, Bharathiar University, Department of Biotechnology, Coimbatore 641046, Tamil Nadu, India. Tel: +422–2425716; fax: +422–2422387; e-mail: [email protected] Received 18 October 2005 Accepted 29 November 2005 Pharmacogenetics and Genomics: July 2006 - Volume 16 - Issue 7 - p 461-468 doi: 10.1097/01.fpc.0000197464.37211.77 Buy Metrics Abstract Background People with genetic variants of butyrylcholinesterase (EC 220.127.116.11, 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. © 2006 Lippincott Williams & Wilkins, Inc.