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, 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, China.
Environ Int. 2020 Jul;140:105762. doi: 10.1016/j.envint.2020.105762. Epub 2020 May 4.
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).
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.
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.
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.
端粒对于维持染色体稳定性和基因组完整性至关重要，而端粒长度对环境应激因素敏感。本研究旨在确定多种金属共同暴露及其与 TERT-CLPTM1L 变体的联合效应对白细胞端粒长度（LTL）的影响。
本研究纳入了一家焦炉厂的 842 名工人，测定了他们的血浆中 23 种金属的浓度和 LTL。采用 Global Screening Array 对 TERT-CLPTM1L 的遗传变异进行了基因分型。采用基于多污染物的统计方法，包括 Bonferroni 校正、向后消除程序和 LASSO 惩罚回归分析，筛选与 LTL 相关的金属。采用广义线性回归模型评估 TERT-CLPTM1L 变体与阳性金属对 LTL 的联合效应。
在单金属模型中，经过 Bonferroni 校正后，血浆中锰（Mn）浓度每增加 1%，LTL 就会相应增加 0.153%（β（95%CI）=0.153（0.075，0.230），P<0.001）。多金属模型和 LASSO 惩罚回归分析均表明，Mn 是唯一能显著预测 LTL 的因素。此外，TERT-CLPTM1L 中的 5 个标签 SNP（rs33954691、rs6554759、rs465498、rs2455393 和 rs31489）与高血浆 Mn（>4.21μg/L）联合作用，增加了 LTL。
本研究在考虑到其他金属共同暴露的情况下，揭示了血浆 Mn 与 LTL 之间独立且正向的关联。TERT-CLPTM1L 变体可进一步增强这种作用。这些结果可能有助于我们深入了解遗传和环境因素对端粒长度的复杂相互作用。需要进一步的实验研究来阐明其潜在机制。
