GENETIC PREDISPOSITION TO ADVERSE CONSEQUENCES OF ANTI-CHOLINESTERASES IN ATYPICAL BCHE CARRIERS

Normal butyrylcholinesterase (BuChE)(1), but not several of its common genetic variants', serves as a scavenger for certain anti-cholinester ases (anti-ChEs). Consideration of this phenomenon becomes urgent in v iew of the large-scale prophylactic use of the anti-ChE, pyridostigmin e, during the 1991 Persian Gulf War, in anticipation of nerve gas atta ck(3) and of the anti-ChE, tacrine, for improving residual cholinergic neurotransmission In Alzheimer's disease patients'. Adverse symptoms were reported for subjects in both groups, but have not been attribute d to specific causes(4,5). Here, we report on an Israeli soldier, homo zygous for 'atypical' BuChE, who suffered severe symptoms following py ridostigmine prophylaxis during the Persian Gulf War. His serum BuChE and recombinant 'atypical' BuChE (ref. 6) were far less sensitive than normal BuChE to inhibition by pyridostigmine and several other carbam ate anti-ChEs. Moreover, atypical BuChE demonstrated 1/200th the affin ity for tacrine of normal BuChE or the related enzyme acetylcholineste rase (AChE). Genetic differences among BuChE variants may thus explain at least some of the adverse responses to anti-ChE therapies.