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学科主题: 公共卫生
题名:
Microsomal epoxide hydrolase (EPHX1) polymorphisms are associated with aberrant promoter methylation of ERCC3 and hematotoxicity in benzene-exposed workers
作者: Xing, Caihong1,2,3; Chen, Qi4; Li, Guilan3; Zhang, Linyuan3; Zheng, Min3; Zou, Zhengyong2; Hou, Lifang5,6; Wang, Qian-Fei2; Liu, Xin4,5; Guo, Xinbiao1
关键词: occupational exposure ; microsomal epoxide hydrolase ; genetic polymorphism ; ERCC3 ; methylation
刊名: ENVIRONMENTAL AND MOLECULAR MUTAGENESIS
发表日期: 2013-07-01
DOI: 10.1002/em.21786
卷: 54, 期:6, 页:397-405
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Environmental Sciences ; Genetics & Heredity ; Toxicology
研究领域[WOS]: Environmental Sciences & Ecology ; Genetics & Heredity ; Toxicology
关键词[WOS]: CHINESE OCCUPATIONAL POPULATION ; DNA-REPAIR GENES ; LUNG-CANCER ; EXPRESSION ; DAMAGE ; RISK ; SUSCEPTIBILITY ; METABOLITES ; COHORT ; HUMANS
英文摘要:

Benzene is an important industrial chemical and widespread environmental pollutant known to induce leukemia and other blood disorders. To be carcinogenic, benzene must be metabolized to produce toxic metabolites. To investigate whether single nucleotide polymorphisms (SNPs) in the metabolic enzyme genes are associated with benzene-induced alterations in DNA methylation and hematotoxicity, we genotyped four commonly studied SNPs in three metabolic enzymes genes CYP1A1, EPHX1 and NQO1; and analyzed promoter DNA methylation status in 11 genes which have been reported to be associated with benzene-induced hematotoxicity (BLM, CYP1A1, EPHX1, ERCC3, NQO1, NUDT1, p15, p16, RAD51, TP53 and WRAP53) in 77 benzene-exposed workers and 25 unexposed controls in China. ERCC3, a DNA repair gene, showed a small but statistically significant increase of promoter DNA methylation in the exposed group compared with the unexposed group (mean +/- SD: 4.73 +/- 3.46% vs. 3.63 +/- 1.96%, P=0.048). We also observed that an increased number of C allele for rs1051740 in EPHX1 was associated with decreased ERCC3 methylation levels in benzene-exposed workers (P-trend=0.001), but not in unexposed controls (P-trend=0.379). Interestingly, another EPHX1 SNP (rs2234922) was associated with lower white blood cell (WBC) counts (P-trend=0.044) in benzene-exposed workers. These associations remained the same when ERCC3 promoter methylation and WBCs were dichotomized according to the 90th percentile (6%) of methylation levels in controls and a leucopenia cutoff (<4 x 10(9)/L), respectively. Our findings suggest that benzene exposure may be associated with hypermethylation in ERCC3, and that genetic variants in EPHX1 may play an important role in epigenetic changes and hematotoxicity among benzene-exposed workers. Environ. Mol. Mutagen. 54:397-405, 2013. (c) 2013 Wiley Periodicals, Inc.

语种: 英语
所属项目编号: 81270612
项目资助者: National Natural Science Foundation of China ; National Institute for Occupational Health and Poison Control, China CDC
WOS记录号: WOS:000321295400003
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/64274
Appears in Collections:北京大学公共卫生学院_期刊论文

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作者单位: 1.Peking Univ, Sch Publ Hlth, Dept Occupat & Environm Hlth Sci, Beijing 100191, Peoples R China
2.Chinese Acad Sci, Beijing Inst Genom, Lab Dis Genom & Individualized Med, Beijing, Peoples R China
3.Chinese Ctr Dis Control & Prevent, Natl Inst Occupat Hlth & Poison Control, Key Lab Chem Safety & Hlth, Beijing, Peoples R China
4.Northwestern Univ, Dept Pediat,Feinberg Sch Med, Mary Ann & J Milburn Smith Child Hlth Res Program, Ann & Robert H Lurie Childrens Hosp Chicago Res C, Chicago, IL 60611 USA
5.Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Chicago, IL 60611 USA
6.Northwestern Univ, Feinberg Sch Med, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA

Recommended Citation:
Xing, Caihong,Chen, Qi,Li, Guilan,et al. Microsomal epoxide hydrolase (EPHX1) polymorphisms are associated with aberrant promoter methylation of ERCC3 and hematotoxicity in benzene-exposed workers[J]. ENVIRONMENTAL AND MOLECULAR MUTAGENESIS,2013,54(6):397-405.
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