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Do mutations in DNMT3A/3B affect global DNA hypomethylation among benzene-exposed workers in Southeast China?: Effects of mutations in DNMT3A/3B on global DNA hypomethylation
- Source :
- Environmental and Molecular Mutagenesis. 58:678-687
- Publication Year :
- 2017
- Publisher :
- Wiley, 2017.
-
Abstract
- 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.
- Subjects :
- 0301 basic medicine
Genetics
Epidemiology
Health, Toxicology and Mutagenesis
Single-nucleotide polymorphism
Mutagen
Biology
medicine.disease_cause
Molecular biology
03 medical and health sciences
chemistry.chemical_compound
030104 developmental biology
0302 clinical medicine
chemistry
030220 oncology & carcinogenesis
DNA methylation
Genotype
medicine
Allele
Restriction fragment length polymorphism
Genetics (clinical)
DNA
DNA hypomethylation
Subjects
Details
- ISSN :
- 08936692
- Volume :
- 58
- Database :
- OpenAIRE
- Journal :
- Environmental and Molecular Mutagenesis
- Accession number :
- edsair.doi...........6becad622a90d3fc1792a4f7e282fd88