Platelet mitochondrial cytochrome c oxidase subunit I variants with benzene poisoning

Abstract

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.

Susceptibility to COVID‐19 in populations with health disparities: Posited involvement of mitochondrial disorder, socioeconomic stress, and pollutants

“…[ 33 ] Mitochondrial cytochrome c oxidase subunit I variants at T6392C, G6962A, and C7196A in platelet mtDNA occurred with chronic benzene poisoning. [ 34 ] In vitro analysis of mitochondria demonstrated bioactivation of benzene to toxic metabolites, which bound to DNA causing an inability of mitochondrial RNA polymerase to transcribe the genome with subsequent inhibition of translation. [ 35 ] Benzene can also inhibit mitochondrial translation most probably because transcription is inhibited, resulting in a lack of mRNA and a subsequent disaggregation of polysomes.…”

Extension of Mitogenome Enrichment Based on Single Long-Range PCR: mtDNAs and Putative Mitochondrial-Derived Peptides of Five Rodent Hibernators

“…The approach produced a ∼ 2,000-fold enrichment of mtDNA before NGS analysis ( Quispe-Tintaya et al, 2013 ; Weissig and Edeas, 2015 ). Alternatively, interfering NUMTs can be excluded from the very start by targeting material naturally depleted of nuDNA such as thrombocytes (cellular mtDNA content of platelets: ∼1.6 copies ( Urata et al, 2008 ; Wang et al, 2018 )) or plasma that was recently reported to contain free-floating mitochondria ( Al Amir Dache et al, 2020 ) and circular mtDNA derived from the haematopoietic system ( Ma et al, 2019 ). The use of plasma DNA as natural source of nuclear depletion is hampered by the fact that direct NGS analysis would produce unnecessary nuDNA reads since extrachromosomal circular DNA was found to be released from tissues into the circulation ( Kumar et al, 2017 ).…”

Impact of chronic benzene poisoning on aberrant mitochondrial DNA methylation: A prospective observational study

“…CBP patients were diagnosed between 2018 and 2021 by the authorized local Occupational Disease Diagnostic Team, with (a) total white blood cell (WBC) counts <4.0 ± 10 9 /L or WBC counts between 4.0 ± 10 9 /L and 4.5 ± 10 9 /L and platelet (PLT) counts <80 ± 10 9 /L, and repeated confirmation of these counts in a peripheral blood sample after a few months; (b) documented benzene exposure as a result of employment in a factory for at least 6 months, (c) exclusion of other known causes of abnormal blood cells counts, such as chloromycetin use and ionizing radiation. The diagnostic criteria for occupational CBP are issued by the Ministry of Health and Family Planning Committee (17). Eligible healthy individuals had normal physical examination results and no history of genetic diseases.…”