title: Genetic Variations in the Promoter of the APE1 Gene Are Associated with DMF-Induced Abnormal Liver Function: A Case-Control Study in a Chinese Population.
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.
authors.affiliation: Kunshan Municipal Center for Disease Prevention and Control, Kunshan 215301, China. 79972002tzm@163.com.
authors.forename: Zhimin
authors.initials: Z
authors.lastname: Tong
authors.affiliation: Kunshan Municipal Center for Disease Prevention and Control, Kunshan 215301, China. shenhuanxi@163.com.|Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Cancer Center, Nanjing Medical University, Nanjing 211166, China. shenhuanxi@163.com.
authors.forename: Huanxi
authors.initials: H
authors.lastname: Shen
authors.affiliation: Department of Integrated Management &amp; Emergency Preparedness and Response, Jiangsu Provincial Center for Disease Prevention and Control, Nanjing 210009, China. Yangdan1997@163.com.
authors.forename: Dandan
authors.initials: D
authors.lastname: Yang
authors.affiliation: Institute of Occupational Disease Prevention, Jiangsu Provincial Center for Disease Prevention and Control, No.172 Jiangsu Road, Nanjing 210009, China. zhangfeng0401@163.com.
authors.forename: Feng
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Institute of Occupational Disease Prevention, Jiangsu Provincial Center for Disease Prevention and Control, No.172 Jiangsu Road, Nanjing 210009, China. baiy@jscdc.cn.
authors.forename: Ying
authors.initials: Y
authors.lastname: Bai
authors.affiliation: The First People's Hospital of Kunshan, Kunshan 215300, China. qianyingbingfeng@163.com.
authors.forename: Qian
authors.initials: Q
authors.lastname: Li
authors.affiliation: Kunshan Municipal Center for Disease Prevention and Control, Kunshan 215301, China. sjian@163.com.
authors.forename: Jian
authors.initials: J
authors.lastname: Shi
authors.affiliation: Institute of Occupational Disease Prevention, Jiangsu Provincial Center for Disease Prevention and Control, No.172 Jiangsu Road, Nanjing 210009, China. hd-zhang@263.net.
authors.forename: Hengdong
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Cancer Center, Nanjing Medical University, Nanjing 211166, China. zhubl@jscdc.cn.|Institute of Occupational Disease Prevention, Jiangsu Provincial Center for Disease Prevention and Control, No.172 Jiangsu Road, Nanjing 210009, China. zhubl@jscdc.cn.
authors.forename: Baoli
authors.initials: B
authors.lastname: Zhu
mesh_terms: D044466:Asian People; D016022:Case-Control Studies; D056486:Chemical and Drug Induced Liver Injury / Q000453:epidemiology*; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase / Q000235:genetics / Q000378:metabolism*; D004126:Dimethylformamide / Q000008:administration & dosage / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005838:Genotype; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D011110:Polymorphism, Genetic
chemical_list: D004126:Dimethylformamide; C085108:APEX1 protein, human; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase
keywords: APE1; N,N-dimethylformamide; XRCC1; hOGG1; polymorphism