Co-exposure to multiple metals, TERT-CLPTM1L variants, and their joint influence on leukocyte telomere length
Objective: Telomere is required for maintaining chromosome stability and genome integrity, while telomere length is sensitive to environmental stressors. We aimed to identify the effects of multiple metals co-exposure as well as their joint effects with TERT-CLPTM1L variants on leukocyte telomere le...
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Format: | Article |
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Elsevier
2020-07-01
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Series: | Environment International |
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Online Access: | http://www.sciencedirect.com/science/article/pii/S0160412019347531 |
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doaj-58b018c4e21e425ba7a790ea79e8c97f |
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record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Yansen Bai Wenshan Fu Xin Guan Xiulong Wu Guyanan Li Wei Wei Yue Feng Hua Meng Hang Li Mengying Li Ming Fu Jiali Jie Chenming Wang Xiaomin Zhang Meian He Huan Guo |
spellingShingle |
Yansen Bai Wenshan Fu Xin Guan Xiulong Wu Guyanan Li Wei Wei Yue Feng Hua Meng Hang Li Mengying Li Ming Fu Jiali Jie Chenming Wang Xiaomin Zhang Meian He Huan Guo Co-exposure to multiple metals, TERT-CLPTM1L variants, and their joint influence on leukocyte telomere length Environment International Telomere length Multiple metals TERT-CLPTM1L Genetic variants |
author_facet |
Yansen Bai Wenshan Fu Xin Guan Xiulong Wu Guyanan Li Wei Wei Yue Feng Hua Meng Hang Li Mengying Li Ming Fu Jiali Jie Chenming Wang Xiaomin Zhang Meian He Huan Guo |
author_sort |
Yansen Bai |
title |
Co-exposure to multiple metals, TERT-CLPTM1L variants, and their joint influence on leukocyte telomere length |
title_short |
Co-exposure to multiple metals, TERT-CLPTM1L variants, and their joint influence on leukocyte telomere length |
title_full |
Co-exposure to multiple metals, TERT-CLPTM1L variants, and their joint influence on leukocyte telomere length |
title_fullStr |
Co-exposure to multiple metals, TERT-CLPTM1L variants, and their joint influence on leukocyte telomere length |
title_full_unstemmed |
Co-exposure to multiple metals, TERT-CLPTM1L variants, and their joint influence on leukocyte telomere length |
title_sort |
co-exposure to multiple metals, tert-clptm1l variants, and their joint influence on leukocyte telomere length |
publisher |
Elsevier |
series |
Environment International |
issn |
0160-4120 |
publishDate |
2020-07-01 |
description |
Objective: Telomere is required for maintaining chromosome stability and genome integrity, while telomere length is sensitive to environmental stressors. We aimed to identify the effects of multiple metals co-exposure as well as their joint effects with TERT-CLPTM1L variants on leukocyte telomere length (LTL). Methods: This study included 842 workers from a coke-oven plant, of whom plasma concentrations of 23 metals and LTL were determined. Genetic variations in TERT-CLPTM1L were genotyped by using the Global Screening Array. Multipollutant-based statistical methods, including the Bonferroni-correction, backward elimination procedure, and LASSO penalized regression analysis, were used to select the LTL-associated metals. Generalized linear regression models were used to evaluate the joint effects of TERT-CLPTM1L variants with positive metal on LTL. Results: Each 1% increase in plasma concentration of manganese (Mn) was significantly associated with a 0.153% increase in LTL [β(95%CI) = 0.153(0.075, 0.230), P < 0.001] in single-metal models after Bonferroni-correction. The multiple-metal models and the LASSO penalized regression analysis both indicated Mn as the sole significant predictor for LTL. Furthermore, 5 tagSNPs (rs33954691, rs6554759, rs465498, rs2455393, and rs31489) in TERT-CLPTM1L with high plasma Mn (>4.21 μg/L) showed joint effects on increasing LTL. Conclusions: Our study revealed the independent and positive association between plasma Mn and LTL when accounting for co-exposure to other metals. This effect can be further enhanced by TERT-CLPTM1L variants. These results may advance our understanding of the complex interplay between genetic and environmental factors on telomere length. Further experimental studies are warranted to elucidate the underlying mechanisms. |
topic |
Telomere length Multiple metals TERT-CLPTM1L Genetic variants |
url |
http://www.sciencedirect.com/science/article/pii/S0160412019347531 |
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doaj-58b018c4e21e425ba7a790ea79e8c97f2020-11-25T03:20:37ZengElsevierEnvironment International0160-41202020-07-01140Co-exposure to multiple metals, TERT-CLPTM1L variants, and their joint influence on leukocyte telomere lengthYansen Bai0Wenshan Fu1Xin Guan2Xiulong Wu3Guyanan Li4Wei Wei5Yue Feng6Hua Meng7Hang Li8Mengying Li9Ming Fu10Jiali Jie11Chenming Wang12Xiaomin Zhang13Meian He14Huan Guo15Department of Occupational and Environmental Health, State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, ChinaDepartment of Occupational and Environmental Health, State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, ChinaDepartment of Occupational and Environmental Health, State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, ChinaDepartment of Occupational and Environmental Health, State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, ChinaDepartment of Occupational and Environmental Health, State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, ChinaDepartment of Occupational and Environmental Health, State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, ChinaDepartment of Occupational and Environmental Health, State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, ChinaDepartment of Occupational and Environmental Health, State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, ChinaDepartment of Occupational and Environmental Health, State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, ChinaDepartment of Occupational and Environmental Health, State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, ChinaDepartment of Occupational and Environmental Health, State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, ChinaDepartment of Occupational and Environmental Health, State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, ChinaDepartment of Occupational and Environmental Health, State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, ChinaDepartment of Occupational and Environmental Health, State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, ChinaDepartment of Occupational and Environmental Health, State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, ChinaCorresponding author at: Department of Occupational and Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Rd, Wuhan 430030, Hubei, China.; Department of Occupational and Environmental Health, State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, ChinaObjective: Telomere is required for maintaining chromosome stability and genome integrity, while telomere length is sensitive to environmental stressors. We aimed to identify the effects of multiple metals co-exposure as well as their joint effects with TERT-CLPTM1L variants on leukocyte telomere length (LTL). Methods: This study included 842 workers from a coke-oven plant, of whom plasma concentrations of 23 metals and LTL were determined. Genetic variations in TERT-CLPTM1L were genotyped by using the Global Screening Array. Multipollutant-based statistical methods, including the Bonferroni-correction, backward elimination procedure, and LASSO penalized regression analysis, were used to select the LTL-associated metals. Generalized linear regression models were used to evaluate the joint effects of TERT-CLPTM1L variants with positive metal on LTL. Results: Each 1% increase in plasma concentration of manganese (Mn) was significantly associated with a 0.153% increase in LTL [β(95%CI) = 0.153(0.075, 0.230), P < 0.001] in single-metal models after Bonferroni-correction. The multiple-metal models and the LASSO penalized regression analysis both indicated Mn as the sole significant predictor for LTL. Furthermore, 5 tagSNPs (rs33954691, rs6554759, rs465498, rs2455393, and rs31489) in TERT-CLPTM1L with high plasma Mn (>4.21 μg/L) showed joint effects on increasing LTL. Conclusions: Our study revealed the independent and positive association between plasma Mn and LTL when accounting for co-exposure to other metals. This effect can be further enhanced by TERT-CLPTM1L variants. These results may advance our understanding of the complex interplay between genetic and environmental factors on telomere length. Further experimental studies are warranted to elucidate the underlying mechanisms.http://www.sciencedirect.com/science/article/pii/S0160412019347531Telomere lengthMultiple metalsTERT-CLPTM1LGenetic variants |