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Dose-related telomere damage associated with the genetic polymorphisms of cGAS/STING signaling pathway in the workers exposed by PAHs
2020
Duan, Xiaoran | Yang, Yongli | Wang, Sihua | Feng, Xiaolei | Wang, Tuanwei | Wang, Pengpeng | Ding, Mingcui | Zhang, Hui | Liu, Bin | Wei, Wan | Yao, Wu | Cui, Liuxin | Zhou, Xiaoshan | Wang, Wei
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.
Show more [+] Less [-]Effect modification by apoptosis-related gene polymorphisms on the associations of phthalate exposure with spermatozoa apoptosis and semen quality
2017
Yang, Pan | Gong, Ya-Jie | Wang, Yi-Xin | Liang, Xin-Xiu | Liu, Qing | Liu, Chong | Chen, Ying-Jun | Sun, Li | Lu, Wen-Qing | Zeng, Qiang
Human studies indicate that phthalate exposure is associated with adverse male reproductive health, and this association may be modified by genetic polymorphisms.We investigated whether apoptosis-related gene polymorphisms modified the associations of phthalate exposure with spermatozoa apoptosis and semen quality.In this Chinese population who sought for semen examination in an infertility clinic, we measured 8 phthalate metabolites in two urine samples to assess the individual's exposure levels. Apoptosis-related gene (Fas, FasL, and caspase3) polymorphisms were performed by real-time PCR. Spermatozoa apoptosis and semen quality parameters were evaluated by Annexin V/PI assay and computer-aided semen analysis, respectively.We found that Fas rs2234767, FasL rs763110, and caspase3 rs12108497 gene polymorphisms significantly modified the associations between urinary phthalate metabolites and spermatozoa apoptosis. For example, urinary monobutyl phthalate (MBP) associated with an increased percentage of Annexin V⁺/PI⁻ spermatozoa of 25.11% (95% CI: 4.08%, 50.53%) were only observed among men with CT/TT genotype of FasL rs763110. In addition, we found that caspase3 rs12108497 gene polymorphisms significantly modified the associations of urinary mono (2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) with decreased sperm concentration and sperm count (both p-values for interactions = 0.02).Our results provided the first evidence that apoptosis-related gene polymorphisms might contribute to the effects of phthalate exposure on male reproductive health.
Show more [+] Less [-]Associations of polycyclic aromatic hydrocarbons exposure and its interaction with XRCC1 genetic polymorphism with lung cancer: A case-control study
2021
Zhou, Shuang | Zhu, Qiuqi | Liu, Huimin | Jiang, Shunli | Zhang, Xu | Peng, Cheng | Yang, Guanlin | Li, Jiaoyuan | Cheng, Liming | Zhong, Rong | Zeng, Qiang | Miao, Xiaoping | Lü, Qing
Humans are extensively exposed to polycyclic aromatic hydrocarbons (PAHs) daily via multiple pathways. Epidemiological studies have demonstrated that occupational exposure to PAHs increases the risk of lung cancer, but related studies in the general population are limited. Hence, we conducted a case-control study among the Chinese general population to investigate the associations between PAHs exposure and lung cancer risk and analyze the modifications of genetic polymorphisms in DNA repair genes. In this study, we enrolled 122 lung cancer cases and 244 healthy controls in Wuhan, China. Urinary PAHs metabolites were determined by gas chromatography-mass spectrometry, and rs25487 in X-ray repair cross-complementation 1 (XRCC1) gene was genotyped by the Agena Bioscience MassARRAY System. Then, multivariable logistic regression models were performed to estimate the potential associations. We found that urinary hydroxynaphthalene (OH-Nap), hydroxyphenanthrene (OH-Phe) and the sum of hydroxy PAHs (∑OH-PAHs) levels were significantly higher in lung cancer cases than those in controls. After adjusting for gender, age, BMI, smoking status, smoking pack-years, drinking status and family history, urinary ∑OH-Nap and ∑OH-Phe levels were positively associated with lung cancer risk, with dose-response relationships. Compared with those in the lowest tertiles, individuals in the highest tertiles of ∑OH-Nap and ∑OH-Phe had a 2.13-fold (95% CI: 1.10, 4.09) and 2.45-fold (95% CI: 1.23, 4.87) increased risk of lung cancer, respectively. Effects of gender, age, smoking status and smoking pack-years on the associations of PAHs exposure with lung cancer risk were shown in the subgroup analysis. Furthermore, associations of urinary ∑OH-Nap and ∑OH-PAHs levels with lung cancer risk were modified by XRCC1 rs25487 (Pᵢₙₜₑᵣₐcₜᵢₒₙ ≤ 0.025), and were more pronounced in wild-types of rs25487. These findings suggest that environmental exposure to naphthalene and phenanthrene is associated with increased lung cancer risk, and polymorphism of XRCC1 rs25487 might modify the naphthalene exposure-related lung cancer effect.
Show more [+] Less [-]Associations of ambient particulate matter with homocysteine metabolism markers and effect modification by B vitamins and MTHFR C677T gene polymorphism
2021
Yang, Bo-Yi | Cao, Ke | Luo, Ya-Na | He, Zhi-Zhou | Guo, Peng-Yue | Ma, Hui-Min | Yang, Mo | Zhou, Yang | Hu, Liwen | Chen, Gong-Bo | Zeng, Xiao-Wen | Yu, Hong-Yao | Yu, Yunjiang | Dong, Guang-Hui
Evidence concerning effects of ambient air pollution on homocysteine (HCY) metabolism is scarce. We aimed to explore the associations between ambient particulate matter (PM) exposure and the HCY metabolism markers and to evaluate effect modifications by folate, vitamin B₁₂, and methylenetetrahyfrofolate reductase (MTHFR) C677T gene polymorphism. Between December 1, 2017 and January 5, 2018, we conducted a panel study in 88 young college students in Guangzhou, China, and received 5 rounds of health examinations. Real-time concentrations of PMs with aerodynamic diameter ≤2.5 (PM₂.₅), ≤1.0 (PM₁.₀), and ≤0.1 (PM₀.₁) were monitored, and the serum HCY metabolism markers (i.e., HCY, S-Adenosylhomocysteine [SAH], and S-Adenosylmethionine [SAM]) were repeatedly measured. We applied linear mixed effect models combined with a distributed lag model to evaluate the associations of PMs with the HCY metabolism markers. We also explored effect modifications of folate, vitamin B₁₂, and the MTHFR C677T polymorphism on the associations. We observed that higher concentrations of PM₂.₅ and PM₁.₀ were associated with higher serum levels of HCY, SAH, SAM, and SAM/SAH ratio (e.g., a 10 μg/m³ increase in PM₂.₅ during lag 0 day and lag 5 day was significantly associated with 1.3–19.4%, 1.3–28.2%, 6.2–64.4%, and 4.8–28.2% increase in HCY, SAH, SAM, and SAM/SAH ratio, respectively). In addition, we observed that the associations of PM₂.₅ with the HCY metabolism markers were stronger in participants with lower B vitamins levels. This study demonstrated that short-term exposure to PM₂.₅ and PM₁.₀ was deleteriously associated with the HCY metabolism markers, especially in people with lower B vitamins levels.
Show more [+] Less [-]Effect modification of CPY2E1 and GSTZ1 genetic polymorphisms on associations between prenatal disinfection by-products exposure and birth outcomes
2018
Zhou, Bin | Yang, Pan | Gong, Ya-Jie | Zeng, Qiang | Lu, Wen-Qing | Miao, Xiao-Ping
Prenatal disinfection by-products (DBPs) exposure is linked with adverse birth outcomes. Genetic susceptibility to DBP metabolism may modify the exposure-outcome associations.To investigate whether CYP2E1 and GSTZ1 genetic polymorphisms modified the associations of prenatal DBP exposures with adverse birth outcomes.Two biomarkers of DBP exposures including trihalomethanes (THMs) in blood and trichloroacetic acid (TCAA) in urine were determined among 426 pregnant women from a Chinese cohort study. CYP2E1 (rs2031920, rs3813867, and rs915906) and GSTZ1 (rs7975) polymorphisms in cord blood were genotyped. Statistical interactions between prenatal DBP exposures and newborns CYP2E1 and GSTZ1 polymorphisms on birth outcomes (birth weight, birth length, and gestational age) were examined by multivariable linear regression with adjustment for potential confounders.We found that newborns CYP2E1 genetic polymorphisms (rs2031920 and rs3813867) modified the associations of maternal blood THMs or urinary TCAA levels with birth outcomes. However, these interactions were nonsignificant after Bonferroni correction for multiple comparisons, except for the interaction between maternal blood BrTHMs [sum of dibromochloromethane (DBCM), bromodichloromethane (BDCM), and bromoform (TBM)] and newborns CYP2E1 gene rs2031920 polymorphisms on birth weight (P for interaction = 0.003).Newborns genetic variations of CYP2E1 rs2031920 may modify the impacts of prenatal BrTHM exposure on birth weight. This finding needs to be further confirmed.
Show more [+] Less [-]Occupational health hazards and wide spectrum of genetic damage by the organic solvent fumes at the workplace: A critical appraisal
2022
Verma, Neha | Pandit, Soumya | Gupta, Piyush Kumar | Kumar, Sanjay | Anil Kumar, | Giri, Shiv Kumar | Yadav, Gulab | Priya, Kanu
Long-term exposure to organic solvents is known to affect human health posing serious occupational hazards. Organic solvents are genotoxic, and they can cause genetic changes in the exposed employees' somatic or germ cells. Chemicals such as benzene, toluene, and gasoline induce an excessive amount of genotoxicity results either in genetic polymorphism or culminates in deleterious mutations when concentration crosses the threshold limits. The impact of genotoxicity is directly related to the time of exposure, types, and quantum of solvent. Genotoxicity affects almost all the physiological systems, but the most vulnerable ones are the nervous system, reproductive system, and blood circulatory system. Based on the available literature report, we propose to evaluate the outcomes of such chemicals on the exposed humans at the workplace. Attempts would be made to ascertain if the long-term exposure makes a person resistant to such chemicals. This may seem to be a far-fetched idea but has not been studied. The health prospect of this study is envisaged to complement the already existing data facilitating a deeper understanding of the genotoxicity across the population. This would also demonstrate if it correlates with the demographic profile of the population and contributes to comorbidity and epidemiology.
Show more [+] Less [-]Impact of mannose-binding lectin gene polymorphism on lung functions among workers exposed to airborne Aspergillus in a wastewater treatment plant in Egypt
2022
Saad-Hussein, Amal | Moubarz, Gehan | Mahdy-Abdallah, Heba | Helmy, Mona Adel
In this study, the risk of Aspergillus (Asp.) positivity and its respiratory health impacts on wastewater treatment plant (WWTP) workers were studied. In addition, it identified the geno-susceptibility role of mannose-binding lectin 2 (MBL2) gene polymorphisms and the mannose-binding lectin (MBL) serum levels on the pulmonary functions of the Asp.-positive workers. Pulmonary function tests (PFTs) were performed for 89 workers from a selected WWTP, after exclusion of the smokers. Molecular identification of Asp. blood positivity was done by 18S rRNA sequencing. Determination of MBL2 gene polymorphism and estimation of MBL serum levels were done. PFTs revealed abnormalities in 49.2% of the workers. Asp. was positive in 42.5% of the workers with different species. Among the Asp.-positive workers, 6.5% of the workers were with obstructive PFTs, 12.9% with restriction, and 22.6% with combined PFT abnormalities. MBL2 genotyping showed that wild genotype AA was common (68.5%) among Asp.-positive workers compared to the other genotypes. This allele, whether homozygous or heterozygous, was significantly associated with decline in PFTs of the exposed workers. MBL serum levels were significantly lower in workers with obstructive, restrictive, and combined PFT abnormalities compared to those with normal PFTs, and in the workers with Asp.-positive species than the Asp.-negative workers. Moreover, it was significantly lower in workers with Asp. fumigatus compared to that in the workers with other Asp. species, and in the Asp.-positive workers with homozygous or heterozygous A allele compared to that in the Asp.-positive workers with homozygous B allele. Working in a WWTP can be associated with impaired PFTs due to exposure to airborne fungi. MBL2 genotyping showed that Asp.-positive workers with homozygous or heterozygous A allele were at risk to develop decline in their PFTs.
Show more [+] Less [-]Maternal Δ-aminolevulinic acid dehydratase 1-2 genotype enhances fetal lead exposure and increases the susceptibility to the development of cerebral palsy
2020
Abdel Hamid, Omaima Ibrahim | Khayal, Eman El-Sayed Hassan | Tolba, Sabry Abdel Rahman | Orabi, Eman Elshahat
Limited epidemiologic studies questioned the association between pre- and postnatal lead exposure and the development of cerebral palsy (CP). Moreover, the genotypes of δ-aminolevulinic acid dehydratase (δ-ALAD) in CP patients and their mothers and their association to the blood lead levels (BLLs) were not previously studied. This study aimed to evaluate the association between δ-ALAD gene polymorphism and BLL in cases of CP and their mothers. A case control study was carried out on 23 CP cases and equal number of healthy matched controls. The mothers of the included children were asked to answer a questionnaire involving the baseline clinical and demographic characteristics. Also, questionnaires were done to detect the sources of environmental lead exposure and screen lead exposure during the pregnancy period. BLL, δ-ALAD enzyme activity, and genetic analysis for ALAD G177C were done for each child and his mother. There was significant (p < 0.001) elevation of BLL in CP cases and their mothers that was positively correlated (r = 0.436, p < 0.05). There were progressive decreases in δ-ALAD activity with increasing BLL in both children and mothers (p < 0.05). There were non-significant (p > 0.05) differences between CP and the control group regarding frequency of ALAD G177C genotypes, while there was a significant (p = 0.04) increase in the frequency of ALAD 1-2 (GC) genotype in the mothers of the CP group associated with high BLL and significant decrease in δ-ALAD activity (p < 0.001). The study can indicate the significance of δ-ALAD gene polymorphism in the prenatal exposure to lead and the affection of the developing brain, pointing to the importance of controlling lead in pregnant women especially those with ALAD 1-2 genotype.
Show more [+] Less [-]Biochemical and genotoxic effects in women exposed to pesticides in Southern Ecuador
2019
Arévalo-Jaramillo, Paulina | Idrobo, Alicia | Salcedo, Lorena | Cabrera, Andrea | Vintimilla, Andrea | Carrión, Mayra | Bailon-Moscoso, Natalia
Toxicity refers to the potential of a substance such as a pesticide to cause damage to the structure or functions of an exposed organism. Pesticides can lead to harmful biological effects in exposed animals and their offspring over the medium and long term. They can affect the immunological, nervous, endocrine, and reproductive systems. DNA damage has also been linked to exposure to pesticides, and this damage can cause abortions, degenerative diseases, and cancer. The aim of this work was to establish whether women who are indirectly exposed to pesticides exhibit a compromised health status, including genotoxic effect. Women exposed indirectly to pesticides in Chimchanga and Colaisaca in the south of Ecuador underwent hematological and biochemical tests and micronucleus assay in buccal cells. The subjects were also genotyped for GSTM1, GSTT1, GSTP1, and PON1 polymorphisms, which can modify an individual’s capacity to metabolize pesticides and relation with damage of DNA. The study revealed hepatic toxicity in Colaisaca women (AST and ALT) and an increase in the rate of micronucleus (MN) in Colaisaca individuals. In addition, genetic polymorphisms in PON1 and GSTP1 showed effects of modulating the frequency of karyolytic cells, karyorrhectic cells, and condensed chromatin cells.
Show more [+] Less [-]Microsatellite polymorphism of Trifolium pratense population at the conditions of radioactive and chemical contamination of soil (Komi republic, Russia)
2018
Rybak, Anna V. | Belykh, Elena S. | Maystrenko, Tatiana A. | Velegzhaninov, Ilya O.
There is no clear understanding of microevolutionary changes in natural populations of plants and animals due to anthropogenic contamination of the environment with toxicants and mutagens. But such data are necessary to forecast long-term effects of human activity. In this research, we studied genetic polymorphism in T. pratense sampled from seven sites varying in radioactive and chemical soil contamination in the vicinity of Vodny settlement (Komi, Russia). Analysis of five SSR loci was shown to be similar in a whole (N), mean (Nₐ) and effective (Nₑ) numbers of alleles, heterozygosity indexes (Hₒ and Hₑ), and the Shannon index (I). Difference in the private allele numbers was registered: the most contaminated site has 5 and others from 0 up 2 private alleles. No difference was found in the genetic structure of T. pratense population growing at the conditions of radioactive and chemical contamination. The Bayesian analysis provided evidence of a single cluster (K = 1) due to a similar genetic structure of samples, while AMOVA results demonstrated a high variability within individuals (75%) and a low variability (1%) among groups of T. pratense from sites that differ in the contamination level. Thus, the long-term radioactive and heavy metal contamination of soil did not result in significant microevolutionary changes in T. pratense population.
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