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  • The repeat sequence TTAGGG of telomere

    2019-10-09

    The repeat sequence “TTAGGG” of telomere could be directly recognized by TERF1. TERF1 is indispensable for the maintenance of telomere Prednisone structure and integrity (Tan et al., 2017). Trf1 genetic depletion in vivo induces a persistent DNA damage response and telomere uncapping, which effectively blocks the growth of aggressive and rapidly growing lung tumors in Trp53-deficient KrasG12V mice, suggesting that TERF1 has an important role in telomere replication, telomere capping and mitosis (Garcia-Beccaria et al., 2015). This study found that ChEs activity of TERF1 rs3863242 (AA) and (GG) genotype were higher than that of (AG) genotype, the differences had statistically significance (P = 0.017); due to the P value was closely to the critical value, therefore, GG was merged with the heterozygous genotype, the ChEs activity of the AG+GG genotypes for TERF1 rs3863242 polymorphism was statistically lower than that of the AA genotypes in control group (P = 0.020). However, the ChEs activity of the AG+GG genotypes for TERF1 rs3863242 polymorphism was not statistically significant differences than that of the AA genotypes in exposure group (P = 0.279). Multivariable analysis showed that the ChEs activities of AG and GG genotypes for TERF1 rs3863242 genetic polymorphisms were lower than that of wild genotype (AA) (t = − 2.416, P = 0.016), suggesting wild genotype (AA) was probably a protective factor of ChEs. However, Savage et al. (2006) found that the risk of aplastic anemia increased with the TERF1 rs3863242 AA genotype. The relationship of TERF1 rs3863242 genetic polymorphisms and other tumors has not been reported. The mechanism is not clear. There is still possible that the TERF1 genetic polymorphism is an important protective factor for AA and our study should be followed up with a larger study. The main function of POT1 is to protect telomere DNA from damage and plays an important role in the maintenance of telomeres. At present, the genetic polymorphism of POT1 is mainly focused on the tumor. So fur there is only a few lines of research on omethoate-exposed workers. It was reported that the risk of breast cancer increased by 1.48 times with the POT1 rs1034794 T-allele, suggesting that POT1–03 (rs33964002) A-allele has a protective effect on the risk of breast cancer (Shen et al., 2012). However, there is no research on the relationship of POT1 rs1034794, POT1 rs10250202 and ChEs activity. This study indicated that ChEs activity had no statistically significant differences among the different genotypes of POT1 rs1034794 and rs10250202 genetic polymorphisms. Even though ChEs activity associations with POT1 SNPs are possible, our data show that POT1 genetic variants are unlikely to substantially affect overall ChEs activity. The up-regulation of the TERT gene in human cancers leads to telomerase activation, which contributes to the growth advantage and survival of tumor cells. Liu et al. (2017) showed that TERT rs2736098 was graded strength for evidence of a relationship with lung cancer risk. There are some studies indicated that TERT rs2736098 A-allele is associated with a significantly increased risk of lung cancer (Wu et al., 2013) and bladder cancer (Singh et al., 2014). A meta-analysis confirmed that no significant association between the TERT rs2736098 polymorphism and cancer risk (Zhang et al., 2012). However, the result showed the rs2736098 was significantly related with an increased cancer risk by removal two studies (OR = 1.337, 95% CI: 1.183–1.511). In this study, we found that ChEs activity had no statistically significant differences among the different genotypes of TERT rs2736098 genetic polymorphism. The effects of agender, age, smoking and drinking on ChEs activity were also analyzed in this study. Univariate analysis showed that male, smoking and drinking had an effect on ChEs activity in two groups (P < 0.05), and showed that age had an effect on ChEs activity in the control group (P < 0.05). Interestingly, the ChEs activity of smokers was greater than that in nonsmokers. Nicotine is the main components of tobacco, there is no doubt that exposure to nicotine during pregnancy has severe impact on the abnormal development of fetus (Zhang et al., 2018). However, some studies demonstrated that nicotine has an antioxidant effect and can be used to treat certain neurodegenerative disease (Newman et al., 2002). Multivariate analysis explored that male agender was the potential protection factors of ChEs activity which was consistent with univariate analysis results. On the other hand, the ChEs activity in men was greater than that in women, which suggested the women were susceptible population to omethoate. Previous studies have demonstrated that prenatal exposure to OPs had higher risk for adverse neurodevelopment (Zhang et al., 2014). Sokoloff et al. (2016) found that 93% of pregnant women had at least one dialkyl phosphate (DAP) being detected in their urine. Multivariate analysis explored that drinking was the potential protect factor of ChEs activity. Prickett et al. (2004) found that there is a J-shaped risk curve for association of alcohol consumption with oxidative status of plasma. The antioxidant activity was found in plasma after moderate alcohol consumption; but excessive drinking seemed to increase the pro-oxidant activity. We assume alcohol play a similar role in omethoate-exposed workers. In addition, we also analyzed the association between work duration and ChEs activity, results showed that working duration had no significant effect on ChEs activity.