Association of BER and NER pathway polymorphism haplotypes and micronucleus frequencies with global DNA methylation in benzene-exposed workers of China: Effects of DNA repair genes polymorphisms on genetic damage

The base excision repair (BER) pathway and nucleotide excision repair (NER) pathway play important roles in the repair of benzene-induced genetic damage, and the effects of polymorphisms in these pathways on genetic damage and global DNA methylation are of great interest. Ten single nucleotide polym...

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Published in:Mutation research. Genetic toxicology and environmental mutagenesis 2019-03, Vol.839, p.13
Main Authors: Zhang, Guang-Hui, Ren, Jing-Chao, Luo, Mengkai, Cui, Junpeng, Du, Yanqiu, Yang, Daokun, Cui, Shouming, Wang, Xiao, Wu, Weidong, Cao, Jia, Xia, Zhao-Lin
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container_title Mutation research. Genetic toxicology and environmental mutagenesis
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creator Zhang, Guang-Hui
Ren, Jing-Chao
Luo, Mengkai
Cui, Junpeng
Du, Yanqiu
Yang, Daokun
Cui, Shouming
Wang, Xiao
Wu, Weidong
Cao, Jia
Xia, Zhao-Lin
description The base excision repair (BER) pathway and nucleotide excision repair (NER) pathway play important roles in the repair of benzene-induced genetic damage, and the effects of polymorphisms in these pathways on genetic damage and global DNA methylation are of great interest. Ten single nucleotide polymorphisms (SNPs) in the BER (XRCC1: rs25489, rs25487; APE1: rs1130409) and NER pathways (XPA: rs1800975; XPC: rs2228000, rs2228002; XPD: rs13181, rs1799793; XPG: rs17655; ERCC1: rs3212986) were analyzed by a Kompetitive allele-specific PCR (KASP) assay to find associations with cytokinesis-block micronucleus (MN) frequency and global DNA methylation in 294 shoe factory workers and 102 control participants. Workers who possessed the following genotypes were associated with high MN frequency: rs25487 AA (FR (95% CI): 1.50 (1.16,1.9), p = 0.002, reference GG); rs1130409 GG (FR (95% CI): 1.28 (1.05,1.55), p = 0.010, reference TT); rs17655 GC (FR (95% CI): 1.18 (1.02,1.38), p = 0.038, reference GG); and rs3212986 TT (FR (95% CI): 1.55 (1.31,1.83), p 
doi_str_mv 10.1016/j.mrgentox.2019.01.006
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Ten single nucleotide polymorphisms (SNPs) in the BER (XRCC1: rs25489, rs25487; APE1: rs1130409) and NER pathways (XPA: rs1800975; XPC: rs2228000, rs2228002; XPD: rs13181, rs1799793; XPG: rs17655; ERCC1: rs3212986) were analyzed by a Kompetitive allele-specific PCR (KASP) assay to find associations with cytokinesis-block micronucleus (MN) frequency and global DNA methylation in 294 shoe factory workers and 102 control participants. Workers who possessed the following genotypes were associated with high MN frequency: rs25487 AA (FR (95% CI): 1.50 (1.16,1.9), p = 0.002, reference GG); rs1130409 GG (FR (95% CI): 1.28 (1.05,1.55), p = 0.010, reference TT); rs17655 GC (FR (95% CI): 1.18 (1.02,1.38), p = 0.038, reference GG); and rs3212986 TT (FR (95% CI): 1.55 (1.31,1.83), p &lt; 0.001, reference GG). Workers with four and three mutant alleles showed 3.72-fold (OR (95% CI): 3.72 (1.34, 10.03), p = 0.009) and 2.48-fold (OR (95% CI): 2.48 (1.27, 4.88), p = 0.008) increased risk of genetic damage compared with workers with no or one mutant allele, and a dose-response relationship was found by the trend test (p = 0.006). The rs1130409 variant allele (GG+GT) was associated with low global DNA methylation (β=-0.20, 95% CI: -0.42, 0.03, p = 0.045). In benzene-exposed workers, BER and NER pathway polymorphism haplotypes are associated with different levels of chromosome damage and had little effect on global DNA methylation.</description><identifier>EISSN: 1879-3592</identifier><identifier>DOI: 10.1016/j.mrgentox.2019.01.006</identifier><identifier>PMID: 30744808</identifier><language>eng</language><publisher>Netherlands</publisher><ispartof>Mutation research. Genetic toxicology and environmental mutagenesis, 2019-03, Vol.839, p.13</ispartof><rights>Copyright © 2019. 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Genetic toxicology and environmental mutagenesis</title><addtitle>Mutat Res Genet Toxicol Environ Mutagen</addtitle><description>The base excision repair (BER) pathway and nucleotide excision repair (NER) pathway play important roles in the repair of benzene-induced genetic damage, and the effects of polymorphisms in these pathways on genetic damage and global DNA methylation are of great interest. Ten single nucleotide polymorphisms (SNPs) in the BER (XRCC1: rs25489, rs25487; APE1: rs1130409) and NER pathways (XPA: rs1800975; XPC: rs2228000, rs2228002; XPD: rs13181, rs1799793; XPG: rs17655; ERCC1: rs3212986) were analyzed by a Kompetitive allele-specific PCR (KASP) assay to find associations with cytokinesis-block micronucleus (MN) frequency and global DNA methylation in 294 shoe factory workers and 102 control participants. Workers who possessed the following genotypes were associated with high MN frequency: rs25487 AA (FR (95% CI): 1.50 (1.16,1.9), p = 0.002, reference GG); rs1130409 GG (FR (95% CI): 1.28 (1.05,1.55), p = 0.010, reference TT); rs17655 GC (FR (95% CI): 1.18 (1.02,1.38), p = 0.038, reference GG); and rs3212986 TT (FR (95% CI): 1.55 (1.31,1.83), p &lt; 0.001, reference GG). Workers with four and three mutant alleles showed 3.72-fold (OR (95% CI): 3.72 (1.34, 10.03), p = 0.009) and 2.48-fold (OR (95% CI): 2.48 (1.27, 4.88), p = 0.008) increased risk of genetic damage compared with workers with no or one mutant allele, and a dose-response relationship was found by the trend test (p = 0.006). The rs1130409 variant allele (GG+GT) was associated with low global DNA methylation (β=-0.20, 95% CI: -0.42, 0.03, p = 0.045). 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Genetic toxicology and environmental mutagenesis</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhang, Guang-Hui</au><au>Ren, Jing-Chao</au><au>Luo, Mengkai</au><au>Cui, Junpeng</au><au>Du, Yanqiu</au><au>Yang, Daokun</au><au>Cui, Shouming</au><au>Wang, Xiao</au><au>Wu, Weidong</au><au>Cao, Jia</au><au>Xia, Zhao-Lin</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Association of BER and NER pathway polymorphism haplotypes and micronucleus frequencies with global DNA methylation in benzene-exposed workers of China: Effects of DNA repair genes polymorphisms on genetic damage</atitle><jtitle>Mutation research. Genetic toxicology and environmental mutagenesis</jtitle><addtitle>Mutat Res Genet Toxicol Environ Mutagen</addtitle><date>2019-03</date><risdate>2019</risdate><volume>839</volume><spage>13</spage><pages>13-</pages><eissn>1879-3592</eissn><abstract>The base excision repair (BER) pathway and nucleotide excision repair (NER) pathway play important roles in the repair of benzene-induced genetic damage, and the effects of polymorphisms in these pathways on genetic damage and global DNA methylation are of great interest. Ten single nucleotide polymorphisms (SNPs) in the BER (XRCC1: rs25489, rs25487; APE1: rs1130409) and NER pathways (XPA: rs1800975; XPC: rs2228000, rs2228002; XPD: rs13181, rs1799793; XPG: rs17655; ERCC1: rs3212986) were analyzed by a Kompetitive allele-specific PCR (KASP) assay to find associations with cytokinesis-block micronucleus (MN) frequency and global DNA methylation in 294 shoe factory workers and 102 control participants. Workers who possessed the following genotypes were associated with high MN frequency: rs25487 AA (FR (95% CI): 1.50 (1.16,1.9), p = 0.002, reference GG); rs1130409 GG (FR (95% CI): 1.28 (1.05,1.55), p = 0.010, reference TT); rs17655 GC (FR (95% CI): 1.18 (1.02,1.38), p = 0.038, reference GG); and rs3212986 TT (FR (95% CI): 1.55 (1.31,1.83), p &lt; 0.001, reference GG). Workers with four and three mutant alleles showed 3.72-fold (OR (95% CI): 3.72 (1.34, 10.03), p = 0.009) and 2.48-fold (OR (95% CI): 2.48 (1.27, 4.88), p = 0.008) increased risk of genetic damage compared with workers with no or one mutant allele, and a dose-response relationship was found by the trend test (p = 0.006). The rs1130409 variant allele (GG+GT) was associated with low global DNA methylation (β=-0.20, 95% CI: -0.42, 0.03, p = 0.045). In benzene-exposed workers, BER and NER pathway polymorphism haplotypes are associated with different levels of chromosome damage and had little effect on global DNA methylation.</abstract><cop>Netherlands</cop><pmid>30744808</pmid><doi>10.1016/j.mrgentox.2019.01.006</doi></addata></record>
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title Association of BER and NER pathway polymorphism haplotypes and micronucleus frequencies with global DNA methylation in benzene-exposed workers of China: Effects of DNA repair genes polymorphisms on genetic damage
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