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Co-exposure to multiple metals, TERT-CLPTM1L variants, and their joint influence on leukocyte telomere length
Highlights Increased plasma manganese level is positively associated with telomere length. Multipollutant associations suggest manganese as a sole predictor for telomere length. Manganese has joint effects with TERT-CLPTM1L variants on increasing telomere length. This study offered clues for the early prevention of telomere shortening related diseases.
Abstract 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.
Co-exposure to multiple metals, TERT-CLPTM1L variants, and their joint influence on leukocyte telomere length
Highlights Increased plasma manganese level is positively associated with telomere length. Multipollutant associations suggest manganese as a sole predictor for telomere length. Manganese has joint effects with TERT-CLPTM1L variants on increasing telomere length. This study offered clues for the early prevention of telomere shortening related diseases.
Abstract 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.
Co-exposure to multiple metals, TERT-CLPTM1L variants, and their joint influence on leukocyte telomere length
Bai, Yansen (author) / Fu, Wenshan (author) / Guan, Xin (author) / Wu, Xiulong (author) / Li, Guyanan (author) / Wei, Wei (author) / Feng, Yue (author) / Meng, Hua (author) / Li, Hang (author) / Li, Mengying (author)
2020-04-22
Article (Journal)
Electronic Resource
English
Telomere length , Multiple metals , <italic>TERT</italic>-<italic>CLPTM1L</italic> , Genetic variants , Al , aluminum , As , arsenic , Ba , barium , Cd , cadmium , Co , cobalt , Cr , chromium , Cu , copper , Fe , iron , Mn , manganese , Mo , molybdenum , Ni , nickel , Pb , lead , Rb , rubidium , Sb , antimony , Se , selenium , Sn , tin , Sr , strontium , Ti , titanium , Tl , thallium , U , uranium , V , vanadium , W , tungsten , Zn , zinc , BMI , body mass index , BPDE-Alb , benzo[a]pyrene-r-7,t-8,t-9,c-10-tetrahydotetrol-albumin adducts , CIs , confidence intervals , <italic>CLPTM1L</italic> , cleft lip and palate transmembrane protein 1-like , CV , coefficient of variation , eQTL , the expression Quantitative Trait Loci , GC–MS , gas chromatography-mass spectrometry , GTEx , Genotype-Tissue Expression , GWAS , genome-wide association study , HWE , Hardy-Weinberg equilibrium , ICP-MS , inductively coupled plasma-mass spectrometry , LASSO , least absolute shrinkage and selection operator , LD , linkage disequilibrium , LOD , limit of detection , LTL , leukocyte telomere length , MAF , minor allele frequency , Mn-SOD , manganese superoxide dismutase , MSE , mean squared error , OH-PAHs , monohydroxy polycyclic aromatic hydrocarbons , ΣOH-PAHs , the sum concentrations of OH-PAHs , PAH , polycyclic aromatic hydrocarbons , Q , quartile , QC , quality control , SD , standard deviation , STE , standard error , SNP , single nucleotide polymorphism , <italic>TERT</italic> , telomerase reverse transcriptase
| Elsevier | 2020
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