Co-exposure to multiple metals, TERT-CLPTM1L variants, and their joint influence on leukocyte telomere length

被引:24
作者
Bai, Yansen [1 ]
Fu, Wenshan [1 ]
Guan, Xin [1 ]
Wu, Xiulong [1 ]
Li, Guyanan [1 ]
Wei, Wei [1 ]
Feng, Yue [1 ]
Meng, Hua [1 ]
Li, Hang [1 ]
Li, Mengying [1 ]
Fu, Ming [1 ]
Jie, Jiali [1 ]
Wang, Chenming [1 ]
Zhang, Xiaomin [1 ]
He, Meian [1 ]
Gun, Huan [1 ]
机构
[1] Huazhong Univ Sci & Technol, Dept Occupat & Environm Hlth, State Key Lab Environm Hlth Incubating, Sch Publ Hlth,Tongji Med Coll, Wuhan 430030, Peoples R China
基金
中国国家自然科学基金;
关键词
Telomere length; Multiple metals; TERT-CLPTM1L; Genetic variants; GENETIC-VARIATION; OXIDATIVE-STRESS; ARSENIC EXPOSURE; ASSOCIATION; PLASMA; MANGANESE; CANCER; DAMAGE; RISK; TERC;
D O I
10.1016/j.envint.2020.105762
中图分类号
X [环境科学、安全科学];
学科分类号
08 ; 0830 ;
摘要
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 [beta(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 mu g/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.
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页数:8
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