谷胱甘肽 S-转移酶 O2 多态性与铜业工人尿液砷形态的关系。
Association between GSTO2 polymorphism and the urinary arsenic profile in copper industry workers.
机构信息
Grup de Mutagènesi, Departament de Genètica i de Microbiologia, Edifici Cn, Facultat de Biociències, Universitat Autònoma de Barcelona, Campus de Bellaterra, 08193 Cerdanyola del Vallès, Bellaterra, Spain.
出版信息
Environ Res. 2010 Jul;110(5):463-8. doi: 10.1016/j.envres.2009.12.005. Epub 2010 Jan 4.
Two members of the recently identified Omega class glutathione S-transferase enzymes (GSTO1 and GSTO2) have been proposed to play a role in the response to arsenic exposure. Therefore, polymorphisms in these genes could be related with variations in the arsenic excretion profile and, consequently, with the individual response to chronic exposure. Exons and flanking regions of GSTO2 gene have been screened in two different ethnic groups (20 Europeans and 20 Chilean Indians), and the urinary arsenic patterns and the GSTO2 Asn142Asp polymorphism have been investigated in 207 copper mine workers occupationally exposed to arsenic. Three polymorphisms of GSTO2 already described were detected in Europeans and Chilean Indians, although with significant different allele frequencies. The genotyping for the Asn142Asp polymorphism revealed that almost no significant association exists between this change and the arsenic excretion profile. However, 142Asp change seems to be correlated with an increase in DMA excretion after age and total urinary arsenic adjustment (OR=3.61; P=0.05). Altogether, our findings indicate that ethnical differences should be taken into account for correlation studies between GST Omega polymorphisms and arsenic susceptibility, and that the 142Asp allozyme could modulate arsenic biotransformation and thereby arsenic toxicity.
两种新近鉴定的 Omega 类谷胱甘肽 S-转移酶(GSTO1 和 GSTO2)成员被认为在砷暴露反应中发挥作用。因此,这些基因的多态性可能与砷排泄模式的变化有关,进而与个体对慢性暴露的反应有关。在两个不同的种族(20 名欧洲人和 20 名智利印第安人)中筛选了 GSTO2 基因的外显子和侧翼区域,并在 207 名职业性接触砷的铜矿工人中调查了 GSTO2 的尿砷模式和 Asn142Asp 多态性。在欧洲人和智利印第安人中检测到了 GSTO2 已描述的三种多态性,但等位基因频率存在显著差异。Asn142Asp 多态性的基因分型表明,这种变化与砷排泄模式之间几乎没有显著的关联。然而,在年龄和总尿砷调整后,142Asp 变化似乎与 DMA 排泄增加相关(OR=3.61;P=0.05)。总之,我们的研究结果表明,在 GST Omega 多态性与砷易感性的相关性研究中,应该考虑种族差异,并且 142Asp 同工酶可能调节砷的生物转化,从而影响砷的毒性。