THE ARG(192) ISOFORM OF PARAOXONASE WITH LOW SARIN-HYDROLYZING ACTIVITY IS DOMINANT IN THE JAPANESE

The high-density-lipoprotein-associated enzyme paraoxonase, which has a role in the detoxification of organophosphorus compounds, is known t o be polymorphic in humans. The Arg(192) isoform of paraoxonase hydrol yzes paraoxon more rapidly than the Gln(192) isoform. However, with re spect to the hydrolysis of toxic nerve agents, such as diazoxon, soman , and sarin, the Arg(192) isoform displays a lower activity than the o ther isoform. To evaluate the possibility that the genetic polymorphis m was involved in the aggravated extent of human injury in the sarin g as poisoning incident in the Tokyo subway in March 1995, we investigat ed the prevalance of this polymorphism in the Japanese population. We found that the Arg(192) allele is more common in the Japanese (allele frequency: 0.66) than in people of other races (ranging 0.24-0.31). In the Japanese, 135 out of the 326 subjects (41.4%) investigated were h omozygous for the Arg(192) allele, which shows a very low hydrolysis a ctivity for sarin. Thus, there seems to be a racial difference in vuln erability to toxic nerve agents, such as sarin. The dominance of the A rg(192) allele in the Japanese population probably worsened the traged y of March 1995 in the Tokyo subway.