Chen Yan, Li Gui-lan, Ji Zhi-ying, Xu Jian-ning, Wu Chun-Ling
College of Public Health, Xinjiang Medical University, Ulumuqi 830054, China.
Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi. 2005 Feb;23(1):1-5.
To explore the relationship between genetic polymorphism of quinone oxidoreductase 1 (NQO1), glutathione S-transferase theta 1 (GSTT1), glutathiones S-transferase mu 1 (GSTM1) and susceptibility to chronic benzene poisoning (BP).
The genotypes of NQO1, GSTT1, GSTM1 for 100 patients with benzene poisoning and 90 workers exposed to benzene who were engaged in the same working time and job title as patients with benzene poisoning were detected by PCR-RFLP and multi-PCR.
There was a 2.82-fold (95% CI: 1.42 approximately 5.58, P < 0.05) increased risk of BP in the subjects with NQO1 C609T mutation genotype (T/T) compared with those carrying heterozygous (C/T) and wild type (C/C), and there was a 2.94-fold (95% CI: 1.25 approximately 6.90, P < 0.05) increased risk of BP in the subjects with NQO1 C609T T/T genotype compared with those carrying C/C genotype. The subjects with GSTT1 null genotype had a 1.91-fold (95% CI: 1.05 approximately 3.45, P < 0.05) increased risk of BP compared with those with GSTT1 non-null genotype. The interaction of two genes showed that there was a increased risk of BP in subjects with any two genotypes of NQO1 C609T T/T genotype and GSTT1 null genotype and GSTM1 null genotype, compared to the individual with any two genotypes of NQO1 C609T C/C genotype and GSTT1 non-null genotype and GSTM1 non-null genotype. The interaction of three genes showed that there was a 20.41-fold (95% CI: 3.79 approximately 111.11, P < 0.01) increased risk of BP in subjects with NQO1 C609T T/T genotype and GSTT1 null genotype and GSTM1 null genotype compared with those carrying NQO1 C609T C/T genotype and C/C genotype and GSTT1 non-null genotype and GSTM1 non-null genotype.
The interaction of multi-genes may be an important role to BP. The genetic polymorphisms of 3 genes (NQO1, GSTT1 and GSTM1) led to declining of detoxifying ability in benzene metabolism, so the individual with NQO1 C609T T/T genotype, GSTT1 null genotype and GSTM1 null genotype is most susceptive to benzene. The results were consistent with that of the theoretic presumption. It could be suggested as a biomarker to assess the risk of benzene poisoning for individuals.
探讨醌氧化还原酶1（NQO1）、谷胱甘肽S-转移酶θ1（GSTT1）、谷胱甘肽S-转移酶μ1（GSTM1）基因多态性与慢性苯中毒（BP）易感性的关系。
采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）及多重PCR技术，检测100例苯中毒患者及90例与苯中毒患者工作时间和工种相同的苯接触工人的NQO1、GSTT1、GSTM1基因分型。
与携带杂合子（C/T）和野生型（C/C）的个体相比，NQO1基因C609T突变基因型（T/T）的个体患BP的风险增加了2.82倍（95%可信区间：1.42至5.58，P<0.05）；与携带C/C基因型的个体相比，NQO1基因C609T T/T基因型的个体患BP的风险增加了2.94倍（95%可信区间：1.25至6.90，P<0.05）。与GSTT1非缺失基因型个体相比，GSTT1缺失基因型个体患BP的风险增加了1.91倍（95%可信区间：1.05至3.45，P<0.05）。两个基因的相互作用表明，与NQO1基因C609T C/C基因型、GSTT1非缺失基因型和GSTM1非缺失基因型的个体相比，NQO1基因C609T T/T基因型、GSTT1缺失基因型和GSTM1缺失基因型中任意两种基因型的个体患BP的风险增加。三个基因的相互作用表明，与携带NQO1基因C609T C/T基因型、C/C基因型、GSTT1非缺失基因型和GSTM1非缺失基因型的个体相比，NQO1基因C609T T/T基因型、GSTT1缺失基因型和GSTM1缺失基因型的个体患BP的风险增加了20.41倍（95%可信区间：3.79至111.11，P<0.01）。
多基因相互作用可能在BP发生中起重要作用。3个基因（NQO1、GSTT1和GSTM1）的基因多态性导致苯代谢解毒能力下降，因此NQO1基因C609T T/T基因型、GSTT1缺失基因型和GSTM1缺失基因型的个体对苯最易感。结果与理论推测一致。可作为评估个体苯中毒风险的生物标志物。
