The Relationship Between HIF1α and Clock Gene Expression in Patients with Obstructive Sleep Apnea

Mar 18, 2022Nature and science of sleep

How Low Oxygen Response and Body Clock Genes Are Linked in People with Obstructive Sleep Apnea

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Abstract

The morning-evening variation in mRNA expression in patients with (OSA) increased significantly by 23% compared to those without OSA.

Gene expression levels of several clock genes decreased with increased apnea hypopnea index (AHI).
In participants with nocturnal hypoxemia (NH), the morning-evening variation of specific clock genes was upregulated by 16%, 14%, and 25%.
The morning-evening variation of HIF1α was positively correlated with certain clock gene levels and negatively correlated with blood oxygen saturation levels.
Patients with OSA or NH may experience circadian rhythm disorders linked to hypoxia-induced changes in gene expression.

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PURPOSE: In this study, we aimed to investigate the precise relationship between hypoxia-inducible factor 1α (HIF1α), , and .

METHODS: We recruited 21 patients with OSA and 22 age-matched controls who underwent polysomnography and had their peripheral blood collected on the evening before and the morning after sleep. OSA was defined as an apnea hypopnea index (AHI) ≥15 events/h. Patients in which T90 > 0 were defined as having nocturnal hypoxemia (NH) and were referred to as the NH group. The mRNA levels ofand several clock genes (s,, andwere determined by RT-qPCR. The percentage difference in gene expression levels when compared between the morning and evening was then determined as referred to as morning-evening variation (MEV). HIF1α, HIF1β Timeles Clock, Bmal1, Per1, Per2, Per3, Cry1, Cry2, Ck1δ, Rorα, NR1D1NPAS2)

RESULTS: The MEV formRNA expression in OSA patients increased significantly by 23% (= 0.008) when compared to patients without OSA. The gene expression levels of(= 0.038) and(= 0.012) decreased with AHI. The MEV of, andmRNA levels were upregulated by 16% (= 0.006), 14% (= 0.027), and 25% (= 0.005), respectively, in participants with NH when compared to those without NH. Furthermore, the MEV formRNA levels was positively correlated with the MEV of, andmRNA levels (= 0.638,< 0.001;= 0.327,= 0.002;= 0.332,= 0.001, respectively) and negatively correlated with LSpO(= -0.464,=0.009) and Mean SpO(= -0.500,= 0.003). HIF1α P Timeless P Cry2P Bmal1, Rorα HIF1α P P P HIF1α Bmal1, Cry1CK1δ R P R P R P R P R P2 2

CONCLUSION: Our data suggest that patients with OSA or NH tend to develop circadian rhythm disorders that may be induced by the hypoxia-mediated augmentation ofgene expression in OSA. HIF1α

Key numbers

23%

Increase in HIF1α MEV

Morning-evening variation of HIF1α mRNA expression in patients vs. controls

25%

Upregulation of clock genes

MEV increase in clock genes in NH patients compared to those without NH

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The Relationship Between HIF1α and Clock Gene Expression in Patients with Obstructive Sleep Apnea

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