Dose-related telomere damage associated with the genetic polymorphisms of cGAS/STING signaling pathway in the workers exposed by PAHs. (May 2020) - Duan, Xiaoran
Abstract: Telomeres are located at the end of eukaryotic chromosomes and vulnerable to exogenous chemical compounds. Exposure to coke oven emissions (COEs) leads to a dose-related telomere damage, and such chromosomal damage might trigger the cGAS / STING signaling pathway which plays an important role in immune surveillance. However, the relationship between the genetic variations in the cGAS / STING signaling pathway and telomere damage in the COEs-exposure workers has not been investigated. Therefore, we recruited 544 coke oven workers and 238 healthy control participants, and determined the level of COEs exposure, concentration of urinary 1-hydroxypyrene (1-OHPYR), genetic polymorphisms and telomere length. The results showed that the telomere length significantly decreased from the control-to high-exposure groups as defined by the external exposure level ( P < 0.05). The results also indicated that STING rs7447927 CC, cGAS rs34413328 AA, and cGAS rs610913 AA could inhibit telomere shortening in the exposure group ( P < 0.05), and cGAS rs34413328, urine 1-OHPYR and cumulative exposure dose (CED) had a significant association with telomere length by generalized linear model. In conclusion, telomere shortening was a combined consequence of short-term exposure, long-term exposure, and genetic variations among the COEs-exposure workers. Graphical abstract: Image 1 Highlights: Urine 1-OHPYR was negatively related to telomere length. Telomere length was associated with the total cumulative exposure dose. Rs34413328 AA could slow down telomere shortening in the coke oven workers.