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Background: Polycyclic aromatic hydrocarbons (PAHs) exposure had been reported to be a risk factor of mtDNAcn in our early study. However, the effect of metabolic enzymes' genetic polymorphisms on mtDNAcn in PAHs-Exposure workers has not been fully evaluated., Aim: The aim of the study was to explore the effect of metabolic enzymes' genetic polymorphisms on mtDNAcn in PAHs-Exposure., Methods and Results: We investigated the effects of metabolic enzymes' genetic polymorphisms on mtDNAcn among 544 coke oven workers and 238 office staffs. The mtDNAcn of peripheral blood leukocytes was measured using the Real-time quantitative polymerase chain reaction (PCR) method. PCR and restriction fragment length was used to detect five polymorphisms in GSTT1, GSTM1, GSTP1 rs1695, CYP2E1 rs6413432, and CYP2E1 rs3813867. The mtDNAcn in peripheral blood leukocytes was significantly lower in the exposure group than that in the control group (p < .001). The 1-OHPYR had an increasing trend with the genotypes AA→AG → GG of GSTP1 rs1695 in the control group. Generalized linear model indicated that the influencing factors of mtDNAcn were PAHs-exposure [β (95% CI) = -0.420 (-0.469, -0.372), p < .001], male [β (95% CI) = -0.058 (-0.103, -0.012), p = .013], and AA genotype for GSTP1 rs1695 [β (95% CI) = -0.051 (-0.095, -0.008), p = .020]., Conclusion: The individuals carrying the AA genotype of GSTP1 rs1695 may have a lower mtDNAcn due to their weaker detoxification of PAHs., (© 2021 The Authors. Cancer Reports published by Wiley Periodicals LLC.)

Objective: The aim of this study was to explore the association between genetic variations in telomere pathway genes and the level of hydrogen peroxide (H 2 O 2 ) in omethoate exposure workers., Methods: A total of 180 omethoate exposure workers and 115 healthy controls were recruited. The level of H 2 O 2 in plasma was determined with molybdenic acid colorimetry. Polymerase chain reaction and restriction fragment length was used to detect polymorphisms in POT1 rs1034794, POT1 rs10250202, TERF1 rs3863242, and TERT rs2736098., Results: The level of H 2 O 2 in exposure group (4.26 ± 0.71) was significantly higher than that in control group (3.29 ± 0.46). Generalized linear models indicated that risk factors for the increase H 2 O 2 level were exposure [β(95 % CI) = 0.951 (0.806, 1.096), P < 0.001] and AA + AT genotype in POT1 rs034794 [β(95 % CI) = 0.397 (0.049, 0.745), P = 0.025]., Conclusion: The increase H 2 O 2 level was associated with omethoate exposure and AA + AT genotypes in POT1 gene rs1034794. It provided a new idea that polymorphisms in telomere pathway genes may indirectly regulate telomere length by influencing oxidative stress., (Copyright © 2020. Published by Elsevier B.V.)

Telomeres are located at the end of eukaryotic chromosomes and vulnerable to exogenous chemical compounds. Exposure to coke oven emissions (COEs) leads to a dose-related telomere damage, and such chromosomal damage might trigger the cGAS/STING signaling pathway which plays an important role in immune surveillance. However, the relationship between the genetic variations in the cGAS/STING signaling pathway and telomere damage in the COEs-exposure workers has not been investigated. Therefore, we recruited 544 coke oven workers and 238 healthy control participants, and determined the level of COEs exposure, concentration of urinary 1-hydroxypyrene (1-OHPYR), genetic polymorphisms and telomere length. The results showed that the telomere length significantly decreased from the control-to high-exposure groups as defined by the external exposure level (P < 0.05). The results also indicated that STING rs7447927 CC, cGAS rs34413328 AA, and cGAS rs610913 AA could inhibit telomere shortening in the exposure group (P < 0.05), and cGAS rs34413328, urine 1-OHPYR and cumulative exposure dose (CED) had a significant association with telomere length by generalized linear model. In conclusion, telomere shortening was a combined consequence of short-term exposure, long-term exposure, and genetic variations among the COEs-exposure workers., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Telomere length was found to be associated with omethoate exposure and polymorphisms in certain genes among occupational workers. However, whether the polymorphisms in telomere-binding protein genes influence telomere length remains unclear. To explore the correlation between telomere length and polymorphisms in telomere-binding protein genes, telomere length in peripheral blood leukocytes was determined by real-time quantitative polymerase chain reaction in 180 omethoate-exposed workers and 115 healthy controls. Polymorphisms in 10 pairs of alleles were detected using flight mass spectrometry or polymerase chain reaction-restriction fragment length polymorphism technique. The results showed that individuals with GG genotype in TRF 1 rs3863242 had longer telomere lengths than those with AG + AA genotype in the control group ( p  = 0.005). The multiple regression analysis suggested that both omethoate exposure ( b  = 0.526, p  < 0.001) and TRF 1 rs3863242 GG ( b  = 0.220, p  = 0.002) were related to a longer telomere length. In conclusion, GG genotype in TRF 1 rs3863242 is linked to prolongation of telomere length, and individuals with GG genotype are recommended to strengthen health protection in a Chinese occupational omethoate-exposed population.

Peripheral blood leukocyte telomere length in omethoate-exposed workers is related to environmental exposure and single nucleotide polymorphisms (SNPs) in genes including p21, GSTM1, miR-145, etc. However, the roles of SNPs in tankyrase (TNKS) gene in telomere length are still unknown. The aim of this study was to explore the association between SNPs in TNKS gene and telomere length in omethoate-exposed workers. Telomere length in peripheral blood leukocyte DNA from 180 omethoate-exposed workers and 115 healthy controls was measured using Real-time quantitative polymerase chain reaction (PCR). Genotyping of the selected functional and susceptible SNPs was performed by the flight mass spectrometry based on PCR and single-base extension. The analysis of covariance was performed to find effects of SNPs on telomere length. Generalized linear models were used to analyze the environment, gene, and interaction on telomere length. The results showed that telomere length in the CG + CC genotypes in rs1055328 in TNKS gene was significantly longer than that in the wild homozygous GG genotype both in exposure group (P = 0.017) and in control group (P = 0.038) after adjusting the covariates. The variables kept in the generalized linear models included omethoate-exposure (β = 0.580, P = 0.001) and rs1055328 (CG + CC) in TNKS gene (β = 0.339, P = 0.002). The study suggests that the prolongation of telomere length is associated with omethoate-exposure and the CG + CC genotypes in rs1055328 in TNKS gene., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Coke oven emissions (COEs), confirmed human carcinogens, are mainly composed of polycyclic aromatic hydrocarbons (PAHs). Telomere shortening in blood leukocytes has been associated with COEs, and polymorphisms in metabolic enzymes. However, the relationship between polymorphisms in telomere related genes and telomere shortening in COEs exposed workers has never been evaluated. Therefore, we measured telomere length and mRNA expression levels of telomere-binding proteins (TBPs) by qPCR method in leucocyte from 544 COEs exposed workers and 238 office staffs (referents). Flight mass spectrometry was used to perform the genotyping of selected functional and susceptible SNPs. The results showed that the telomere length in the exposure group 0.75(0.51,1.08) was significantly shorter than that in the control group 1.05(0.76,1.44) (P < 0.001). The mRNA expression levels of TPP1, TERF1 and TERF2 genes in the exposure group were significantly lower than those in the control group (P < 0.05), the mRNA expression level of POT1 in the exposure group was significantly higher than that in the control group (P < 0.05). We used the wild homozygous genotype as a reference, subjects carrying TERT rs2736109 AA, TERT rs3215401 CC and TERT rs2736100 GT + GG genotypes had significantly longer telomere length in the exposure group (P < 0.05). In conclusion, the workers exposed to COEs had shorter telomere length, which was regulated by the TPP1, TERF1, TERF2 and POT1 genes expression levels, and the gene polymorphisms of TERT gene were associated with the telomere length among PAHs-exposure workers., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objectives: The aim of this study was to investigate the association between coke oven emissions (COEs) exposure and total antioxidant capacity (T-AOC), and to explore whether genetic variations in metabolic enzyme genes GSTT1, GSTM1, GSTP1, and CYP2E1 can affect these associations in coke oven workers., Methods: 536 coke oven workers and 238 healthy controls were recruited. T-AOC of plasma was determined with kit. Five polymorphic loci of GSTT1 (+/-), GSTM1 (+/-), GSTP1 rs1695, CYP2E1 rs6413432 and CYP2E1 rs3813867 were detected by polymerase chain reaction and restriction fragment length polymorphism., Results: This study shows that the T-AOC in exposure group (12.02 ± 4.72) was significantly lower than that in control group (15.32 ± 7.19) (P < 0.01), and the COEs exposure could decrease the T-AOC of coke oven workers significantly [β(95% CI) = -2.663 (-4.538,-0.787), P < 0.001]. The T-AOC of female was lower than that of male in exposed and control groups (P < 0.001). The T-AOC was higher in GSTM1 (-) individuals than in GSTM1 (+) individuals in the control group (P = 0.037). The T-AOC with the AG genotype in GSTP1 rs1695 polymorphism was higher than that of the GG genotype in the control group (P = 0.043). The generalized linear model results showed that the risk factors for the decrease of T-AOC include GSTT1 (+) (b = -0.999, P = 0.009), female (b = -2.875, P < 0.01), COEs-exposed (b = -2.712, P = 0.004), GSTM1 (+) (b = -1.814, P = 0.008), and interactions of GSTM1 (+) and COEs-exposed (b = 1.872, P=0.024)., Conclusions: The risk factors for the decrease of T-AOC include GSTT1 (+), female, COEs-exposed, GSTM1 (+), and interactions of GSTM1 (+) and COEs-exposed., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Omethoate is an organophosphorus pesticide that poses a major health hazard, especially DNA damage. The purpose of this study was to investigate the factors affecting telomere length in workers exposed to omethoate by analyzing the interaction between cell cycle gene polymorphism and environmental factors. The exposure group consisted of 118 workers exposed to omethoate for 8-10 years, the control group comprised 115 healthy people without occupational toxicant exposure history. The telomere length of genomic DNA from peripheral blood leucocyte was determined with real-time PCR. Polymerase chain reaction and restriction fragment length polymorphism was used to detect the polymorphisms in p 53, p 21 and MDM 2 gene. The telomere length in the (CA + AA) genotypes for p 21 rs1801270 polymorphism was longer than that in the CC genotype in control group ( P  = 0.015). The generalized linear model analysis indicated the interaction of the p 21 rs1801270 polymorphic (CA + AA) genotypes and smoking has a significant effect on telomere length (β = -0.258, P  = 0.085). The prolongation of telomere length in omethoate-exposed workers was associated with genotypes (CA + AA) of p 21 rs1801270, and interactions of (CA + AA) genotypes and smoking factor.

Objective: The aim of this study was to explore the association between telomere length and metabolizing enzyme gene polymorphisms and environmental factors in omethoate-exposed workers., Methods: The gene-environment interactions were analyzed with generalized linear model method., Results: The relative telomere lengths in the individuals with GSTM1-deletion were longer than that in non-deletion genotype in the control group (P = 0.011); the relative telomere lengths with GG+AG genotypes in GSTP1 rs1695 were longer than that of AA genotype in the exposure group (P = 0.039). The interaction between the GG+AG genotypes in GSTP1 rs1695 and smoking exposure had significant effect on telomere length (P < 0.05)., Conclusions: The prolongation of relative telomere length in omethoate-exposed workers was associated with GSTM1-deletion, GG+AG genotypes, and interactions of GG+AG genotypes and smoking factor.

Omethoate, an organophosphorous pesticide, can cause a variety of health effects, especially the decrease of cholinesterase activity. The aim of this study is to explore the association of genetic polymorphisms of telomere binding proteins with cholinesterase activity in omethoate-exposed population. Cholinesterase activities in whole blood, red blood cell and plasma were detected using acetylthiocholine and dithio-bis-(nitrobenzoic acid) method; Genetic Genotyping of POT1 rs1034794, POT1 rs10250202, TERF1 rs3863242 and TERT rs2736098 were performed with PCR-RFLP. The cholinesterase activities of whole blood, red blood cells and plasma in exposure group are significantly lower than that of the control group (P < 0.001). Multivariate analysis indicates that exposure group (b = - 1.016, P < 0.001), agender (b = 0.365, P < 0.001), drinking (b = 0.271, P = 0.004) and TERF1rs3863242 (b = - 0.368, P = 0.016) had an impact on cholinesterase activities. The results suggest that individual carrying AG+GG genotypes in TERF1 gene rs3863242 polymorphism were susceptible to damage in cholinesterase induced by omethoate., (Copyright © 2018 Elsevier Inc. All rights reserved.)