血小板线粒体细胞色素c氧化酶亚基I变异与苯中毒
Platelet mitochondrial cytochrome c oxidase subunit I variants with benzene poisoning.
作者信息
Wang Dianpeng, Yang Xiangli, Zhang Yanfang, Lin Dafeng, Li Paimao, Zhang Zhiming, Huang Xianqing, Gu Dayong, Loo Jacky Fong-Chuen
机构信息
Shenzhen Prevention and Treatment Center for Occupational Diseases, Shenzhen 518020, China.
Shenzhen International Travel Health Care Center and Shenzhen Academy of Inspection and Quarantine, Shenzhen 518033, China.
出版信息
J Thorac Dis. 2018 Dec;10(12):6811-6818. doi: 10.21037/jtd.2018.11.82.
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 mitochondrial 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.
背景
慢性苯中毒（CBP）是最常见的慢性职业中毒之一，与线粒体氧化损伤有关，并导致患肺癌等呼吸系统疾病的风险增加。细胞色素c氧化酶亚基I（COI）是通过清除活性氧（ROS）在氧化损伤调节中起重要作用的关键酶之一。本研究调查了COI基因变异与CBP风险之间的关系。
方法
我们调查了44名被诊断为CBP的非吸烟患者和57名年龄在23至60岁之间的未接触过CBP的非吸烟对照者，了解他们的工作经历、生活方式和病历等背景信息。用乙二胺四乙酸（EDTA）管采集外周血（2 mL），并从采集的血液中纯化血小板。通过聚合酶链反应（PCR）和测序分析COI的变异。采用多变量线性回归分析评估CBP暴露与变异之间的关联。
结果
线粒体DNA（mtDNA）T6392C、G6962变异在44例CBP组患者中的发生频率分别为10例、7例，高于对照组57例中的4例、2例，提示这些变异可能是CBP的危险因素[比值比（OR）3.897，95%可信区间（CI）：1.131 - 13.425，P = 0.023；OR 5.203，95%CI：1.024 - 26.442，P = 0.034]。患者与对照样本的血小板mtDNA中COI变异，包括T6392C和G6962A，存在显著差异（P < 0.05）。同时，mtDNA C7196A变异在44例对照组中的发生频率为13例，高于CBP组患者57例中的2例，提示该变异可能是CBP的保护因素（OR 6.205，95%CI：1.320 - 29.162，P = 0.010）。
结论
我们的研究表明，血小板mtDNA变异中的T6392C、G6962A和C7196A在CBP的病因学中起重要作用，并有助于开发用于CBP诊断的分子生物标志物。
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