Downregulation of GPX1 Gene Expression in Electronic Cigarette Users Compared to Non-Smokers
Keywords:
Antioxidant, Downregulation, Electronic Cigarettes, Gene Expression, Glutathione Peroxidase 1 (GPX1), Oxidative Stress
Abstract
Electronic cigarette (e-cigarette) use is often perceived as a safer alternative to conventional smoking, but its biomolecular impact is poorly understood. Oxidative stress from aerosol exposure is detected through changes in antioxidant gene expression, like Glutathione Peroxidase 1 (GPX1). This quantitative cross-sectional study analyzed 72 blood-derived RNA isolates (36 e-cigarette users; 36 non-smokers) to evaluate peripheral blood leukocyte GPX1 gene expression as a marker of oxidative stress. Relative GPX1 expression was quantified via qPCR normalized to GAPDH using the 2⁻ΔΔCt method. Groups were compared using the Mann–Whitney U test, unpaired t-test on log10-transformed data, and multivariable linear regression adjusted for age. E-cigarette users showed significantly lower GPX1 expression than non-smokers (median 0.92 vs. 1.65; Mann–Whitney U, p=0.03; t-test, p=0.035). This difference remained significant in the 18–24-year subgroup (p=0.041), with multivariable regression confirming e-cigarette use as an independent predictor of GPX1 downregulation (β=-0.284, p=0.038). These findings suggest that e-cigarette exposure may impair antioxidant defenses and disrupt systemic redox homeostasis.
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References
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Seo, Y. S., Park, J. M., Kim, J. H., & Lee, M. Y. (2023). Cigarette Smoke-Induced Reactive Oxygen Species Formation: A Concise Review. Antioxidants, 12(9), 1732. doi: 10.3390/ANTIOX12091732
Sharifi-Rad, M., Anil Kumar, N. V., Zucca, P., Varoni, E. M., Dini, L., Panzarini, E., Rajkovic, J., Tsouh Fokou, P. V., Azzini, E., Peluso, I., Prakash Mishra, A., Nigam, M., El Rayess, Y., Beyrouthy, M. El, Polito, L., Iriti, M., Martins, N., Martorell, M., Docea, A. O., …
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Vlahos, R., & Bozinovski, S. (2013). Glutathione peroxidase-1 as a novel therapeutic target for COPD. doi: 10.1179/1351000213Y.0000000053
World Health Organization. (2023). Electronic cigarettes (E-cigarettes). https://www.who.int/publications/i/item/WPR-2024-DHP-001
Al-Zahrani, M. H., & Almutairi, N. M. (2023). Genetic Polymorphisms of GSTM1 and GPX1 Genes and Smoking Susceptibility in the Saudi Population. Journal of Pharmacy & Bioallied Sciences, 15(4), 180. doi: 10.4103/JPBS.JPBS_365_23
Camenga, D. R., & Klein, J. D. (2016). Tobacco Use Disorders. Child and Adolescent Psychiatric Clinics of North America, 25(3), 445–460. doi: 10.1016/j.chc.2016.02.003
Carnevale, R., Sciarretta, S., Violi, F., Nocella, C., Loffredo, L., Perri, L., Peruzzi, M., Marullo, A. G. M., De Falco, E., Chimenti, I., Valenti, V., Biondi-Zoccai, G., & Frati, G. (2016). Acute Impact of Tobacco vs Electronic Cigarette Smoking on Oxidative Stress and Vascular Function. Chest, 150(3), 606–612. doi: 10.1016/J.CHEST.2016.04.012
Chitteti, R., Zuniga-Hertz, J. P., Masso-Silva, J. A., Shin, J., Niesman, I., Bojanowski, C. M., Kumar, A. J., Hepokoski, M., Crotty Alexander, L. E., Patel, H. H., & Roth, D. M. (2025). E-cigarette-induced changes in cell stress and mitochondrial function. Free Radical Biology and Medicine, 228, 329–338. doi: 10.1016/J.FREERADBIOMED.2025.01.004
Christensen, C. H., Chang, J. T., Rostron, B. L., Hammad, H. T., van Bemmel, D. M., Del Valle-Pinero, A. Y., Wang, B., Mishina, E. V, Faulcon, L. M., DePina, A., Brown-Baker, N., Kimmel, H. L., Lambert, E., Blount, B. C., Vesper, H. W., Wang, L., Goniewicz, M. L., Hyland, A., Travers, M. J., … Chang, C. M. (2021). Biomarkers of Inflammation and Oxidative Stress Among Adult Former Smoker, Current E-Cigarette Users-Results from Wave 1 PATH Study. doi: 10.1158/1055-9965.EPI-21-0140
Cichońska, D., Król, O., Słomińska, E. M., Kochańska, B., Świetlik, D., Ochocińska, J., & Kusiak, A. (2021). Influence of Electronic Cigarettes on Antioxidant Capacity and Nucleotide Metabolites in Saliva. Toxics, 9(10), 263. doi: 10.3390/TOXICS9100263
Cooper, M., Harrell, M. B., & Perry, C. L. (2016). Comparing young adults to older adults in e-cigarette perceptions and motivations for use: implications for health communication. Health Education Research, 31(4), 429. doi: 10.1093/HER/CYW030
Donohue, J. F. (2006). Ageing, smoking and oxidative stress. Thorax, 61(6), 461. doi: 10.1136/THX.2005.053058
El Shahawy, O., Sherman, S. E., & Palamar, J. J. (2020). High Prevalence of Tobacco Product and E-cigarette Use among Electronic Dance Music Party Attendees. Substance Use & Misuse, 55(10), 1561. doi: 10.1080/10826084.2020.1717536
Emma, R., Caruso, M., Campagna, D., Pulvirenti, R., & Li Volti, G. (2022). The Impact of Tobacco Cigarettes, Vaping Products and Tobacco Heating Products on Oxidative Stress. Antioxidants, 11(9), 1829. doi: 10.3390/ANTIOX11091829
Fadus, M. C., Smith, T. T., & Squeglia, L. M. (2019). The rise of e-cigarettes, pod mod devices, and JUUL among youth: Factors influencing use, health implications, and downstream effects. In Drug and Alcohol Dependence (Vol. 201, pp. 85–93). Elsevier Ireland Ltd. doi: 10.1016/j.drugalcdep.2019.04.011
Fleming, E., & Luo, Y. (2021). Co-delivery of synergistic antioxidants from food sources for the prevention of oxidative stress. In Journal of Agriculture and Food Research (Vol. 3). Elsevier B.V. doi: 10.1016/j.jafr.2021.100107
Geraghty, P., Baumlin, N., Salathe, M. A., Foronjy, R. F., & D’Armiento, J. M. (2016). Glutathione Peroxidase-1 Suppresses the Unfolded Protein Response upon Cigarette Smoke Exposure. Mediators of Inflammation, 2016. doi: 10.1155/2016/9461289
Gharib, A. F., Eldeen, M. A., Khalifa, A. S., Elsawy, W. H., Eed, E. M., Askary, A. El, Eid, R. A., Soltan, M. A., & Raafat, N. (2021). Assessment of Glutathione Peroxidase-1 (GPX1) Gene Expression as a Specific Diagnostic and Prognostic Biomarker in Malignant Pleural Mesothelioma. Diagnostics, 11(12), 2285. doi: 10.3390/DIAGNOSTICS11122285
Halstead, K. M., Wetzel, E. M., Cho, J. L., & Stanhewicz, A. E. (2023). Sex Differences in Oxidative Stress-Mediated Reductions in Microvascular Endothelial Function in Young Adult e-Cigarette Users. Hypertension, 80(12), 2641–2649. doi: 10.1161/HYPERTENSIONAHA.123.21684/SUPPL_FILE/HYP_HYPE-2023-21684_SUPP3.PDF
Handy, D. E., & Loscalzo, J. (2022). The Role of Glutathione Peroxidase-1 in Health and Disease. Free Radical Biology & Medicine, 188, 146. doi: 10.1016/J.FREERADBIOMED.2022.06.004
Ighodaro, O. M., & Akinloye, O. A. (2018). First line defence antioxidants-superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX): Their fundamental role in the entire antioxidant defence grid. Alexandria Journal of Medicine, 54(4), 287–293. doi: 10.1016/J.AJME.2017.09.001
Jelic, M. D., Mandic, A. D., Maricic, S. M., & Srdjenovic, B. U. (2021). Oxidative stress and its role in cancer. Journal of Cancer Research and Therapeutics, 17(1), 22–28. doi: 10.4103/JCRT.JCRT_862_16
Jerzy, T., & Stimson, G. V. (2023). Estimation of the global number of vapers: 82 million worldwide in 2021. doi: 10.1108/DHS-07-2022-0028
Jerzyński, T., Stimson, G. V., Shapiro, H., & Król, G. (2021). Estimation of the global number of e-cigarette users in 2020. Harm Reduction Journal, 18(1). doi: 10.1186/s12954-021-00556-7
Kosmider, L., Cox, S., Zaciera, M., Kurek, J., Goniewicz, M. L., McRobbie, H., Kimber, C., & Dawkins, L. (2020). Daily exposure to formaldehyde and acetaldehyde and potential health risk associated with use of high and low nicotine e-liquid concentrations. Scientific Reports 2020 10:1, 10(1), 1–10. doi: 10.1038/s41598-020-63292-1
Kuntic, I., Kuntic, · Marin, Oelze, M., Stamm, · Paul, Karpi, A., Kleinert, · Hartmut, Hahad, · Omar, Münzel, T., & Daiber, A. (2023). The role of acrolein for E-cigarette vapour condensate mediated activation of NADPH oxidase in cultured endothelial cells and macrophages. Pflügers Archiv - European Journal of Physiology, 475, 807–821. doi: 10.1007/s00424-023-02825-9
Ling, J., Halim, A., Ahmad, A. F. N. ;, Ahmad, D. ;, Safian, N. ;, Nawi, M., Yn, M., Farid Nazmi, A., Ahmad, D., Ahmad, N., Safian, N., & Nawi, A. M. (2023). Prevalence and Associated Factors of E-Cigarette Use among Adolescents in Southeast Asia: A Systematic Review. International Journal of Environmental Research and Public Health, 20(5), 3883. doi: 10.3390/IJERPH20053883
Lubos, E., Loscalzo, J., & Handy, D. E. (2011). COMPREHENSIVE INVITED REVIEW Glutathione Peroxidase-1 in Health and Disease: From Molecular Mechanisms to Therapeutic Opportunities. Antioxid. Redox Signal, 15, 1957–1997. doi: 10.1089/ars.2010.3586
McCauley, D. M., Gaiha, S. M., Lempert, L. K., & Halpern-Felsher, B. (2022). Adolescents, Young Adults, and Adults Continue to Use E-Cigarette Devices and Flavors Two Years after FDA Discretionary Enforcement. International Journal of Environmental Research and Public Health, 19(14), 8747. doi: 10.3390/IJERPH19148747/S1
Miklós, Z., & Horváth, I. (2023). Horváth, I. The Role of Oxidative Stress and Antioxidants in Cardiovascular Comorbidities in COPD. Antioxidants 2023, 12, 1196. doi: 10.3390/antiox12061196
Cahyo Nugroho, H., Widyagdo, A., Purwanti, R. (2023) Pengetahuan Tentang Dampak Merokok Terhadap Kesehatan Gigi Dan Mulut Dengan Frekuensi Merokok. HIJP : Health Information Jurnal Penelitian, 15(Suplemen), e860. https://myjurnal.poltekkes-kdi.ac.id/index.php/hijp
Pizzino, G., Irrera, N., Cucinotta, M., Pallio, G., Mannino, F., Arcoraci, V., Squadrito, F., Altavilla, D., & Bitto, A. (2017). Oxidative Stress: Harms and Benefits for Human Health. Oxidative Medicine and Cellular Longevity, 2017(1), 8416763. doi: 10.1155/2017/8416763
Roy, A., Rawal, I., Jabbour, S., & Prabhakaran, D. (2017). Tobacco and Cardiovascular Disease: A Summary of Evidence. Disease Control Priorities, Third Edition (Volume 5): Cardiovascular, Respiratory, and Related Disorders, 57–77. doi: 10.1596/978-1-4648-0518-9_CH4
Seo, Y. S., Park, J. M., Kim, J. H., & Lee, M. Y. (2023). Cigarette Smoke-Induced Reactive Oxygen Species Formation: A Concise Review. Antioxidants, 12(9), 1732. doi: 10.3390/ANTIOX12091732
Sharifi-Rad, M., Anil Kumar, N. V., Zucca, P., Varoni, E. M., Dini, L., Panzarini, E., Rajkovic, J., Tsouh Fokou, P. V., Azzini, E., Peluso, I., Prakash Mishra, A., Nigam, M., El Rayess, Y., Beyrouthy, M. El, Polito, L., Iriti, M., Martins, N., Martorell, M., Docea, A. O., …
Sharifi-Rad, J. (2020). Lifestyle, Oxidative Stress, and Antioxidants: Back and Forth in the Pathophysiology of Chronic Diseases. In Frontiers in Physiology (Vol. 11). Frontiers Media S.A. doi: 10.3389/fphys.2020.00694
Sies, H., Berndt, C., & Jones, D. P. (2025). Oxidative Stress. 55, 33. doi: 10.1146/annurev-biochem
U.S Centers for Disease Control and Preventions. (2021). GATS|GLOBAL ADULT TOBACCO SURVEY Fact Sheet Indonesia 2021 GATS Objectives.
Vlahos, R., & Bozinovski, S. (2013). Glutathione peroxidase-1 as a novel therapeutic target for COPD. doi: 10.1179/1351000213Y.0000000053
World Health Organization. (2023). Electronic cigarettes (E-cigarettes). https://www.who.int/publications/i/item/WPR-2024-DHP-001
Published
2026-09-30
How to Cite
Kurnia, J. S., & Hartanti, M. D. (2026). Downregulation of GPX1 Gene Expression in Electronic Cigarette Users Compared to Non-Smokers. Indonesian Journal of Life Sciences, 8(02), 79-89. https://doi.org/10.54250/ijls.v8i02.323
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Cell and Molecular Biology
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