HIF-1α: a potential biomarker in obstructive sleep apnea

Abstract

Obstructive sleep apnea (OSA) is a common breathing disorder characterized by repeated obstruction of the upper airway during sleep. Although polysomnography (PSG) is the widely used method for the diagnosis of OSA, it is a time-consuming and expensive method. Because it requires at least 1 night stay in the hospital and technical personnel are needed. Therefore, it has been focused on biomarkers that can be easily detected in blood for the diagnosis of OSA. Some studies have highlighted the relationship between OSA and cancer in humans, and HIF-1 is an important regulator in this process. KDM3A is a histone demethylase that increases hypoxic gene expression. We aimed to evaluate whether the expression levels of HIF-1α and KDM3A genes could be useful predictors in patients with OSA. Our study included 50 patients with OSA and 50 healthy controls. qRT-PCR was used to detect mRNA levels of HIF-1α, KDM3A, and epithelial-mesenchymal transition (EMT) genes in the leukocyte samples. The expression level of the HIF-1α gene was found significantly higher in the OSA group compared to the controls, and no statistically significant difference was detected in the expression levels of the KDM3A and EMT genes.

Keywords

• Blood- based biomarker
• HIF-1α
• Obstructive sleep apnea
• qRT-PCR.

References

1. Young, T.; Palta, M.; Dempsey, J.; Skatrud, J.; Weber, S.; Badr, S. N Engl J Med. 1993, 328, 1230-5.
2. Chen, Y.H.; Keller, J.K.; Kang, J.H.; Hsieh, H.J.; Lin, H.C. J Clin Sleep Med. 2013, 9, 417-23.
3. Hunyor, I.; Cook, K.M. Am J Physiol Regul Integr Comp Physiol. 2018, 315, R669-R87.
4. Liu, C.; Wang, H.; Zhu, C.; Wang, S. J Clin Lab Anal. 2020, 34, e23545.
5. Toffoli, S.; Michiels, C. FEBS J. 2008, 275, 2991-3002.
6. Zhao, M.; Wang, S.; Zuo, A.; Zhang, J.; Wen, W.; Jiang, W. et al. Cell Mol Biol Lett. 2021, 26, 40.
7. Campos-Rodriguez, F.; Martinez-Garcia, M.A.; Martinez, M.; Duran-Cantolla, J.; de la Pena, M.; Masdeu, M.J. et al. Am J Respir Crit Care Med. 2013, 187, 99-105.
8. Marshall, N.S.; Wong, K.K., Cullen, S.R., Knuiman, M.W.; Grunstein, R.R. J Clin Sleep Med. 2014, 10, 355-62.

9. Ali, M.; Kowkuntla, S.; Delloro, D.J.; Galambos, C.; Hathi, D.; Janz, S. et al. Am J Physiol Regul Integr Comp Physiol. 2019, 316, R678-R86.
10. Gallego-Martin, T.; Farre, R.; Almendros, I.; Gonzalez-Obeso, E.; Obeso, A. Eur Respir J. 2017, 49, 1602111.
11. Malec, V.; Gottschald, O.R.; Li, S.; Rose, F.; Seeger, W.; Hanze, J. Free Radic Biol Med. 2010, 48, 1626-35.
12. Martinive, P.; Defresne, F.; Quaghebeur, E.; Daneau, G.; Crokart, N.; Gregoire, V. et al. FEBS J. 2009, 276, 509-18.
13. Toffoli, S.; Roegiers, A.; Feron, O.; Van Steenbrugge, M.; Ninane, N.; Raes, M. et al. Angiogenesis. 2009, 12, 47-67.
14. Wang, Z.; Si, L.Y. Ups J Med Sci. 2013, 118, 65-74.
15. Cao, D.; Hou, M.; Guan, Y.S., Jiang, M.; Yang, Y., Gou, H.F. BMC Cancer. 2009, 9, 432.
16. Turcotte, S., Desrosiers, R.R.; Béliveau, R. J Cell Sci. 2003, 116, 2247-60.
17. Krieg, A.J.; Rankin, E.B.; Chan, D.; Razorenova, O.; Fernandez, S.; Giaccia, A.J. Mol Cell Biol. 2010, 30, 344-53.
18. Cho, H.S.; Toyokawa, G.; Daigo, Y.; Hayami, S.; Masuda, K.; Ikawa, N. et al. 2012. Int J Cancer. 2012, 131, E179-89.
19. Yamada, D.; Kobayashi, S.; Yamamoto, H.; Tomimaru, Y.; Noda, T.; Uemura, M. et al. Ann Surg Oncol. 2012, 19 Suppl 3, S355-64.
20. Uemura, M.; Yamamoto, H.; Takemasa, I.; Mimori, K.; Hemmi, H.; Mizushima, T. et al. Clin Cancer Res. 2010,16, 4636-46.
21. Wang, J.; Wei, Q.; Wang, X.; Tang, S.; Liu, H.; Zhang, F. et al. Genes Dis. 2016, 3, 3-6.
22. Vu, T.; Datta, P.K. Cancers. 2017, 9, 171.
23. Jiang, J.; Tang, Y-l.; Liang X-h. Cancer Biol Ther. 2014, 11,714–723.
24. Merikallio, H.; T T.T.; Paakko, P.; Makitaro, R.; Kaarteenaho, R.; Lehtonen, S. et al. Int J Clin Exp Pathol. 2014, 7, 5846-54.