Zhang Guang-Hui, Lu Ye, Ji Bu-Qiang, Ren Jing-Chao, Sun Pin, Ding Shibin, Liao Xiaoling, Liao Kaiju, Liu Jinyi, Cao Jia, Lan Qing, Rothman Nathaniel, Xia Zhao-Lin
Henan Collaborative Innovation Center of Molecular Diagnosis and Laboratory Medicine, School of Public Health, Xinxiang Medical University, 601 Jinsui Road, Xinxiang, 453003, China.
Department of Occupational Health and Toxicology, School of Public Health, Fudan University, 138 Yixueyuan Road, Shanghai, 200032, China.
Environ Mol Mutagen. 2017 Dec;58(9):678-687. doi: 10.1002/em.22136. Epub 2017 Sep 25.
Global DNA hypomethylation is commonly observed in benzene-exposed workers, but the underlying mechanisms remain unclear. We sought to discover the relationships among reduced white blood cell (WBC) counts, micronuclear (MN) frequency, and global DNA methylation to determine whether there were associations with mutations in DNMT3A/3B. Therefore, we recruited 410 shoe factory workers and 102 controls from Wenzhou in Zhenjiang Province. A Methylated DNA Quantification Kit was used to quantify global DNA methylation, and single nucleotide polymorphisms (SNPs) in DNMT3A (rs36012910, rs1550117, and R882) and DNMT3B (rs1569686, rs2424909, and rs2424913) were identified using the restriction fragment length polymorphism method. A multilinear regression analysis demonstrated that the benzene-exposed workers experienced significant global DNA hypomethylation compared with the controls (β = -0.51, 95% CI: -0.69 to -0.32, P < 0.001). The DNMT3A R882 mutant allele (R882H and R882C) (β = -0.25, 95% CI: -0.54 to 0.04, P = 0.094) and the DNMT3B rs2424909 GG allele (β = -0.37, 95% CI: -0.70 to -0.03, P = 0.031) were significantly associated with global DNA hypomethylation compared with the wild-type genotype after adjusting for confounding factors. Furthermore, the MN frequency in the R882 mutant allele (R882H and R882C) (FR = 1.18, 95% CI: 0.99 to 1.40, P = 0.054) was higher than that of the wild-type. The results imply that hypomethylation occurs due to benzene exposure and that mutations in DNMTs are significantly associated with global DNA methylation, which might have influenced the induction of MN following exposure to benzene. Environ. Mol. Mutagen. 58:678-687, 2017. © 2017 Wiley Periodicals, Inc.
在接触苯的工人中普遍观察到全基因组DNA低甲基化现象，但其潜在机制仍不清楚。我们试图探究白细胞（WBC）计数减少、微核（MN）频率与全基因组DNA甲基化之间的关系，以确定它们是否与DNMT3A/3B突变存在关联。因此，我们从浙江省温州市招募了410名鞋厂工人和102名对照人员。使用甲基化DNA定量试剂盒对全基因组DNA甲基化进行定量，并采用限制性片段长度多态性方法鉴定DNMT3A（rs36012910、rs1550117和R882）和DNMT3B（rs1569686、rs2424909和rs2424913）中的单核苷酸多态性（SNP）。多线性回归分析表明，与对照组相比，接触苯的工人经历了显著的全基因组DNA低甲基化（β = -0.51，95%CI：-0.69至-0.32，P < 0.001）。在调整混杂因素后，与野生型基因型相比，DNMT3A的R882突变等位基因（R882H和R882C）（β = -0.25，95%CI：-0.54至0.04，P = 0.094）和DNMT3B的rs2424909 GG等位基因（β = -0.37，95%CI：-0.70至-0.03，P = 0.031）与全基因组DNA低甲基化显著相关。此外，R882突变等位基因（R882H和R882C）中的MN频率（FR = 1.18，95%CI：0.99至1.40，P = 0.054）高于野生型。结果表明，低甲基化是由于接触苯所致，并且DNMTs中的突变与全基因组DNA甲基化显著相关，这可能影响了接触苯后MN的诱导。《环境与分子诱变》，2017年第58卷，第678 - 687页。© 2017威利期刊公司
