Department of Occupational and Environmental Health, College of Public Health, China Medical University, Shenyang, Liaoning, PR China.
Mutat Res. 2009 Sep-Oct;679(1-2):44-9. doi: 10.1016/j.mrgentox.2009.07.008. Epub 2009 Jul 25.
Individual variability in arsenic metabolism is suggested to be associated with the effects of chronic arsenic exposure on health. Glutathione-S-transferase omega (GSTO) 1 and 2 are known to have the activity of monomethyl arsenate [MMA(V)] reductase, which is the rate-limiting enzyme for the biotransformation of inorganic arsenic. This study was conducted to investigate the relationship between polymorphisms in the GSTO1 and GSTO2 genes and arsenic metabolism and oxidative stress status in Chinese populations chronically exposed to different levels of arsenic in drinking water. Two polymorphisms (GSTO1A140D and GSTO2N142D) with relatively higher mutation frequencies in the Chinese population were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The allele frequencies of 140D and 142D in the entire study population were 0.17 and 0.25, respectively. There were no significant differences in the urinary arsenic profile, the blood reduced glutathione (GSH) levels, the blood superoxide dismutase (SOD) activity, or the urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels between the study subjects with different genotypes of GSTO1A140D or GSTO2N142D. Multivariate analysis revealed that there was no association between the urinary profile or oxidative stress status and the polymorphism of GSTO1A140D or GSTO2N142D. Collectively, polymorphisms in GSTO1 or GSTO2 do not appear to contribute to the large individual variability in arsenic metabolism or susceptibility to arsenicosis.
个体砷代谢的差异被认为与慢性砷暴露对健康的影响有关。谷胱甘肽 S-转移酶ω(GSTO)1 和 2 已知具有单甲基砷酸盐 [MMA(V)] 还原酶的活性,该酶是无机砷生物转化的限速酶。本研究旨在调查 GSTO1 和 GSTO2 基因多态性与中国不同水平饮用水中慢性砷暴露人群砷代谢和氧化应激状态之间的关系。通过聚合酶链反应-限制性片段长度多态性(PCR-RFLP)确定 GSTO1A140D 和 GSTO2N142D 这两种在中国人群中突变频率相对较高的多态性。140D 和 142D 在整个研究人群中的等位基因频率分别为 0.17 和 0.25。GSTO1A140D 或 GSTO2N142D 不同基因型的研究对象之间,尿砷谱、血还原型谷胱甘肽(GSH)水平、血超氧化物歧化酶(SOD)活性或尿 8-羟基-2'-脱氧鸟苷(8-OHdG)水平无显著差异。多变量分析表明,尿谱或氧化应激状态与 GSTO1A140D 或 GSTO2N142D 多态性之间无关联。综上所述,GSTO1 或 GSTO2 基因的多态性似乎不会导致砷代谢或砷中毒易感性的个体差异较大。