Abstract:
Acute or long-term exposure to N,N-dimethylformamide (DMF) can induce abnormal liver function. It is well known that DMF is mainly metabolized in the liver and thereby produces reactive oxygen species (ROS). The base excision repair (BER) pathway is regarded as a very important pathway involved in repairing ROS-induced DNA damage. Several studies have explored the associations between GSTM1, GSTT1, CYP2E1 polymorphisms and DMF-induced abnormal liver function; however, little is known about how common hOGG1, XRCC1 and APE1 polymorphisms and DMF induce abnormal liver function. The purpose of this study was to investigate whether the polymorphisms in the hOGG1 (rs159153 and rs2072668), XRCC1 (rs25487, rs25489, and rs1799782), APE1 (rs1130409 and 1760944) genes in the human BER pathway were associated with the susceptibility to DMF-induced abnormal liver function in a Chinese population. These polymorphisms were genotyped in 123 workers with DMF-induced abnormal liver function and 123 workers with normal liver function. We found that workers with the APE1 rs1760944 TG/GG genotypes had a reduced risk of abnormal liver function, which was more pronounced in the subgroups that were exposed to DMF for <10 years, exposed to ≥10 mg/m³ DMF, never smoked and never drank. In summary, our study supported the hypothesis that the APE1 rs1760944 T > G polymorphism may be associated with DMF-induced abnormal liver function in the Chinese Han population.
摘要:
急性或长期暴露于N,N-二甲基甲酰胺(DMF)可导致肝功能异常。众所周知,DMF主要在肝脏中代谢,从而产生活性氧(ROS)。碱基切除修复(BER)途径被认为是修复ROS诱导的DNA损伤的非常重要的途径。一些研究已经探索了GSTM1,GSTT1,CYP2E1多态性与DMF诱导的异常肝功能之间的关联;然而,关于hOGG1,XRCC1和APE1多态性以及DMF如何引起肝功能异常,人们知之甚少。这项研究的目的是调查是否在hOGG1(rs159153和rs2072668)的多态性,XRCC1(rs25487、rs25489和rs1799782),人类BER途径中的APE1(rs1130409和1760944)基因与中国人群对DMF诱导的肝功能异常的易感性有关。这些多态性在DMF引起的肝功能异常的123名工人和肝功能正常的123名工人中进行了基因分型。我们发现APE1rs1760944TG/GG基因型的工人肝功能异常的风险降低,这在暴露于DMF<10年的亚组中更为明显,暴露于≥10毫克/立方米DMF,从不抽烟,从不喝酒。总之,我们的研究支持以下假设:APE1rs1760944T>G多态性可能与DMF引起的中国汉族人群肝功能异常有关。