MEG3 polymorphisms associated with peripheral blood leukocyte mitochondrial DNA copy number in PAHs-exposure workers

• Published in: Chemosphere (Oxford) Vol. 344; p. 140335
• Main Authors: Li, Xinling, Duan, Xiaoran, Wang, Wei
• Format: Journal Article
• Language: English
• Published: Elsevier Ltd 01.12.2023
• Subjects: Gene polymorphism; lncRNA; MEG3; mtDNA copy number; PAHs; MEG3; PAHs; lncRNA; mtDNA copy number; Gene polymorphism
• ISSN: 0045-6535; 1879-1298
• DOI: 10.1016/j.chemosphere.2023.140335

Epidemiological studies have shown that exposure to Polycyclic aromatic hydrocarbons (PAHs) is associated with reduced mitochondrial DNA copy number (mtDNA-CN). Long non-coding RNA maternally expressed gene 3 (MEG3) is involved in mitochondrial function regulation. However, it is unknown whether single-nucleotide polymorphisms in the MEG3 can regulate the mtDNAcn in PAHs exposed populations. The aim of this study was to examine the effect of MEG3 genetic polymorphisms on the mtDNA-CN in PAHs exposed populations. We recruited 544 coke oven workers and 238 controls using random cluster sampling. High-performance liquid chromatography was used to detect the concentrations of four OH-PAHs (1-hydroxypyrene [1-OHPyr], 1-hydroxynathalene [1-OHNap], 2-hydroxynathalene [2-OHNap], and 3-hydroxyphenanthrene [3-OHPhe]) in urine. The mtDNA-CN of peripheral blood leukocytes was measured using the quantitative polymerase chain reaction method. Sequenom Mass ARRAY matrix-assisted laser desorption/ionization-time of flight mass spectrometry platform was used to detect ten polymorphisms in MEG3. The OH-PAHs levels in the exposure group were significantly higher than those in the control group (P < 0.001). The mtDNA-CN in the exposure group was significantly lower than that in the control group (P < 0.001). A linear regression model revealed that PAHs-exposure (β [95% confidence interval, CI], −0.428 [-0.475, −0.381], P < 0.001), male gender (−0.052 [-0.098, −0.005], P = 0.029), genotype TT for MEG3 rs11859 (−0.088 [-0.142, −0.035], P = 0.001), and genotype GG for MEG3 rs7155428 (−0.114 [-0.210, −0.017], P = 0.021) were associated with decreased mtDNA-CN. PAHs-exposure, male gender, genotype TT for rs11859, and genotype GG for rs7155428 were risk factors for mtDNA-CN. [Display omitted] •Flight mass spectrometry platform was established to detect MEG3 polymorphisms.•PAHs exposure induced the mtDNA-CN decrease.•MEG3 rs11859 TT and rs7155428 GG may be risk factors of the reduction of mtDNA-CN.