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多环芳烃暴露工人中的遗传多态性、端粒结合蛋白的 mRNA 表达水平及其与端粒损伤的关系。

Genetic polymorphisms, mRNA expression levels of telomere-binding proteins, and associates with telomere damage in PAHs-Exposure workers.

机构信息

Biotherapy Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou 450052, Henan, China; Department of Occupational and Environmental Health, College of Public Health, Zhengzhou University, Zhengzhou, 450001, Henan, China.

Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou, 450001, Henan, China.

出版信息

Chemosphere. 2019 Sep;231:442-449. doi: 10.1016/j.chemosphere.2019.05.134. Epub 2019 May 19.

Abstract

Coke oven emissions (COEs), confirmed human carcinogens, are mainly composed of polycyclic aromatic hydrocarbons (PAHs). Telomere shortening in blood leukocytes has been associated with COEs, and polymorphisms in metabolic enzymes. However, the relationship between polymorphisms in telomere related genes and telomere shortening in COEs exposed workers has never been evaluated. Therefore, we measured telomere length and mRNA expression levels of telomere-binding proteins (TBPs) by qPCR method in leucocyte from 544 COEs exposed workers and 238 office staffs (referents). Flight mass spectrometry was used to perform the genotyping of selected functional and susceptible SNPs. The results showed that the telomere length in the exposure group 0.75(0.51,1.08) was significantly shorter than that in the control group 1.05(0.76,1.44) (P < 0.001). The mRNA expression levels of TPP1, TERF1 and TERF2 genes in the exposure group were significantly lower than those in the control group (P < 0.05), the mRNA expression level of POT1 in the exposure group was significantly higher than that in the control group (P < 0.05). We used the wild homozygous genotype as a reference, subjects carrying TERT rs2736109 AA, TERT rs3215401 CC and TERT rs2736100 GT + GG genotypes had significantly longer telomere length in the exposure group (P < 0.05). In conclusion, the workers exposed to COEs had shorter telomere length, which was regulated by the TPP1, TERF1, TERF2 and POT1 genes expression levels, and the gene polymorphisms of TERT gene were associated with the telomere length among PAHs-exposure workers.

摘要

焦炉逸散物(COEs)被确认为人类致癌物,主要由多环芳烃(PAHs)组成。血液白细胞端粒缩短与 COEs 以及代谢酶的多态性有关。然而,端粒相关基因多态性与 COEs 暴露工人端粒缩短之间的关系尚未得到评估。因此,我们通过 qPCR 方法测量了 544 名 COEs 暴露工人和 238 名办公室工作人员(对照)白细胞中的端粒长度和端粒结合蛋白(TBPs)的 mRNA 表达水平。飞行质谱法用于对选定的功能和易感 SNP 进行基因分型。结果表明,暴露组的端粒长度为 0.75(0.51,1.08)明显短于对照组的 1.05(0.76,1.44)(P<0.001)。暴露组中 TPP1、TERF1 和 TERF2 基因的 mRNA 表达水平明显低于对照组(P<0.05),暴露组中 POT1 基因的 mRNA 表达水平明显高于对照组(P<0.05)。我们以野生纯合基因型为参考,携带 TERT rs2736109 AA、TERT rs3215401 CC 和 TERT rs2736100 GT+GG 基因型的受试者在暴露组中具有明显更长的端粒长度(P<0.05)。总之,暴露于 COEs 的工人端粒长度较短,这受 TPP1、TERF1、TERF2 和 POT1 基因表达水平的调节,TERT 基因的基因多态性与 PAHs 暴露工人的端粒长度有关。

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