Platelet mitochondrial cytochrome c oxidase subunit I variants with benzene poisoning.

JOURNAL OF THORACIC DISEASE(2018)

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摘要
Background: Chronic benzene poisoning (CBP) is one of the most common chronic occupational poisoning which is associated with mitochondrial oxidative damage, and lead to increasing risk of respiratory diseases such as lung cancer. Cytochrome c oxidase subunit I (COI) is one of the key enzymes that plays an important role in oxidative damage regulation by eliminating reactive oxygen species (ROS). This study investigated the relationship between COI gene variants and the risk of CBP. Methods: We investigated 44 non-smoking patients who were diagnosed with CBP and 57 unexposed non-smoking controls between the ages of 23 and 60 with their background including work experience, lifestyle and medical records. Peripheral blood (2 mL) was collected in EDTA tube and the platelet was purified from the collected blood. Variants of COI were analyzed by PCR and sequencing. Multivariable linear regression analysis was used to assess the association between CBP exposure and variants. Results: The frequency of the mitochondria] DNA (mtDNA) T6392C, G6962 variants were 10, 7 out of 44 CBP group patients, which was higher when compared to that of 4, 2 out of 57 in the control group, suggesting these variants could be the risk factor for CBP [odds ratio (OR) 3.897, 95% CI: 1.131-13.425, P=0.023; OR 5.203, 95% CI: 1.024-26.442, P=0.034]. There was a significant difference (P<0.05) of COI variants, including T6392C and G6962A, in platelet mtDNA between patients and control samples. Meanwhile, the frequency of the mtDNA C7196A variant were 13 out of 44 control group, which was higher when compared to that of 2 of 57 in the CBP group patients, suggesting this variant could be the protective factor for CBP (OR 6.205, 95% CI: 1.320-29.162, P=0.010). Conclusions: Our study suggests that T6392C, G6962A and C7196A from platelet mtDNA variants play a significant role in the etiology of CBP and facilitate the development of molecular biomarker on CBP diagnosis.
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Chronic benzene poisoning (CBP),mitochondrial DNA (mtDNA) variants,cytochrome c oxidase subunit I (COI),platelet mtDNA
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