Yamasaki Y, Sakamoto K, Watada H, Kajimoto Y, Hori M
First Department of Medicine, Osaka University School of Medicine, Japan.
Hum Genet. 1997 Nov;101(1):67-8. doi: 10.1007/s004390050588.
The high-density-lipoprotein-associated enzyme paraoxonase, which has a role in the detoxification of organophosphorus compounds, is known to be polymorphic in humans. The Arg192 isoform of paraoxonase hydrolyzes paraoxon more rapidly than the Gln192 isoform. However, with respect to the hydrolysis of toxic nerve agents, such as diazoxon, soman, and sarin, the Arg192 isoform displays a lower activity than the other isoform. To evaluate the possibility that the genetic polymorphism was involved in the aggravated extent of human injury in the sarin gas poisoning incident in the Tokyo subway in March 1995, we investigated the prevalance of this polymorphism in the Japanese population. We found that the Arg192 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 homozygous for the Arg192 allele, which shows a very low hydrolysis activity for sarin. Thus, there seems to be a racial difference in vulnerability to toxic nerve agents, such as sarin. The dominance of the Arg192 allele in the Japanese population probably worsened the tragedy of March 1995 in the Tokyo subway.
与高密度脂蛋白相关的对氧磷酶在有机磷化合物解毒过程中发挥作用，已知其在人类中具有多态性。对氧磷酶的精氨酸192同工型比对氧磷酶的谷氨酰胺192同工型更快速地水解对氧磷。然而，就诸如重氮磷、梭曼和沙林等有毒神经毒剂的水解而言，精氨酸192同工型的活性低于其他同工型。为了评估1995年3月东京地铁沙林毒气中毒事件中基因多态性是否与人类伤害的加重程度有关，我们调查了这种多态性在日本人群中的流行情况。我们发现，精氨酸192等位基因在日本人中（等位基因频率：0.66）比在其他种族人群中（范围为0.24 - 0.31）更为常见。在日本人中，326名被调查对象中有135名（41.4%）是精氨酸192等位基因的纯合子，其对沙林的水解活性非常低。因此，对于诸如沙林等有毒神经毒剂的易感性似乎存在种族差异。精氨酸192等位基因在日本人群中的优势可能加剧了1995年3月东京地铁事件的悲剧。
