Pesticides and susceptible populations: People with butyrylcholinesterase genetic variants may be at risk

Butyrylcholinesterase (BChE) scavenges low doses of organophosphorus (for e xample, paraoxon) and carbamate pesticides (for example, carbaryl) and in t his way protects people from the toxic effects of these poisons. The protec tive role of BChE is demonstrated by the finding that pesticide applicators can have reduced BChE activity with no clinical signs of poisoning. The qu estion has arisen whether people with genetic variants of BChE are less pro tected. Seventy-six percent of the population is homozygous for wildtype BC hE, while 24% carry at least one genetic variant allele. Most genetic varia nts of BChE have reduced activity. The clinically most important variant is atypical (D70G) BChE because people with this variant have 2 hours of apne a after receiving a dose of succinylcholine that is intended to paralyze mu scles for 3-5 minutes. In test tube experiments the atypical variant reacts more slowly with all positively charged compounds (for example physostigmi ne, echothiophate). This leaves more toxin available for reaction with acet yl cholinesterase in nerve synapses and predicts that people with atypical BChE will be less protected. Variants with low activity, such as silent BCh E, are predicted to be at increased risk from organophosphorus pesticides b ased on experiments in monkeys and rodents where injection of purified BChE protected animals from the toxic effects of nerve agents. More studies are needed to strengthen the hypothesis that people with genetic variants of B ChE are at higher risk of intoxication from pesticides. (C) 2000 Inter Pres s, Inc.