Guang-Hui Zhang1, Jing-Chao Ren2, Mengkai Luo2, Junpeng Cui2, Yanqiu Du3, Daokun Yang2, Shouming Cui4, Xiao Wang2, Weidong Wu2, Jia Cao5, Zhao-Lin Xia6. 1. Henan Collaborative Innovation Center of Molecular Diagnosis and Laboratory Medicine, School of Public Health, Xinxiang Medical University, 601 Jinsui Road, Xinxiang, 453003, China. Electronic address: zhgh221@163.com. 2. Henan Collaborative Innovation Center of Molecular Diagnosis and Laboratory Medicine, School of Public Health, Xinxiang Medical University, 601 Jinsui Road, Xinxiang, 453003, China. 3. Department of Occupational Health and Toxicology, School of Public Health, Fudan University, 138 Yixueyuan Road, Shanghai, 200032, China. 4. Xinxiang Academy of Occupational Health and Occupational Medicine, 32 Rongjiao Road, Xinxiang, 453003, China. 5. Henan Collaborative Innovation Center of Molecular Diagnosis and Laboratory Medicine, School of Public Health, Xinxiang Medical University, 601 Jinsui Road, Xinxiang, 453003, China. Electronic address: caojia1962@126.com. 6. Department of Occupational Health and Toxicology, School of Public Health, Fudan University, 138 Yixueyuan Road, Shanghai, 200032, China. Electronic address: zlxia@shmu.edu.cn.
Abstract
OBJECTIVE: 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. METHODS: 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. RESULTS: 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 < 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). CONCLUSION: 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.
OBJECTIVE: 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. METHODS: 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. RESULTS: 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 < 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). CONCLUSION: 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.