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Altered HIF-1α, Netrin-1, and Netrin-4 Levels in Obstructive Sleep Apnea: Associations with Intermittent Hypoxia and
Mehmet Erdem1, Tuğba Raika Kıran1, Nurcan Kırıcı Berber2
1Department of Medical Biochemistry, Faculty of Medicine, Malatya Turgut Özal University, Malatya 44210, Türkiye.
Medicina (Kaunas, Lithuania)
|July 28, 2026
Summary
Obstructive sleep apnea (OSA) is linked to higher levels of HIF-1α, Netrin-1, and Netrin-4. These biomarkers correlate with OSA severity and hypoxia, suggesting their role in the condition.
Area of Science:
- Biochemistry
- Sleep Medicine
- Molecular Biology
Background:
- Obstructive sleep apnea (OSA) involves airway collapse, causing intermittent hypoxia, oxidative stress, and inflammation.
- Hypoxia-inducible factor-1α (HIF-1α) is key in hypoxia adaptation.
- Netrin-1 and Netrin-4 roles in OSA-related hypoxia are not well understood.
Purpose of the Study:
- Investigate circulating HIF-1α, Netrin-1, and Netrin-4 levels in OSA patients.
- Assess associations between these biomarkers and OSA severity/hypoxic burden.
Main Methods:
- Included 52 newly diagnosed OSA patients and 26 controls.
- Measured serum HIF-1α, Netrin-1, and Netrin-4 via ELISA.
- Used ROC analysis and correlation/regression analyses with polysomnography data.
Main Results:
- Serum HIF-1α, Netrin-1, and Netrin-4 levels were significantly elevated in OSA patients and increased with severity.
- Biomarkers showed excellent (HIF-1α, Netrin-1) to good (Netrin-4) discriminative ability.
- All biomarkers positively correlated with apnea-hypopnea index (AHI) and T90 (hypoxic burden), independent of BMI, age, gender, CRP, and LDL.
Conclusions:
- Circulating HIF-1α, Netrin-1, and Netrin-4 are elevated in OSA and linked to disease severity and hypoxia.
- Findings suggest intermittent hypoxia activates HIF-1α and Netrin pathways in OSA.
- Netrin family members may serve as biomarkers for hypoxia-related inflammation and endothelial changes in OSA.
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