Clock gene expression is altered in veterans with sleep apnea

Abstract

Clock gene dysregulation has been shown to underlie various sleep disorders and may lead to negative cardio-metabolic outcomes. However, the association between sleep apnea (SA) and core clock gene expression is unclear. We performed a cross-sectional analysis of 49 Veterans enrolled in a study of SA outcomes in veterans with chronic kidney disease, not selected for SA or sleep complaints. All participants underwent full polysomnography and next morning whole blood collection for clock gene expression. We defined SA as an apnea-hypopnea index ≥15 events/h; nocturnal hypoxemia(NH) was defined as ≥10% of total sleep time spent at <90% oxygen saturation. We used quantitative real-time PCR to compare the relative gene expression of clock genes between those with and without SA or NH. Clock genes studied were Bmal1, Ck1δ, Ck1ε, Clock, Cry1, Cry2, NPAS2, Per1, Per2, Per3, Rev-Erb-α, RORα, and Timeless. Our cohort was 90% male, mean age was 71 yr (SD 11), mean body mass index was 30 kg/m2 (SD 5); 41% had SA, and 27% had NH. Compared with those without SA, Per3 expression was reduced by 35% in SA ( P = 0.027). Compared with those without NH, NPAS2, Per1, and Rev-Erb-α expression was reduced in NH (50.4%, P = 0.027; 28.7%, P = 0.014; 31%, P = 0.040, respectively). There was no statistical difference in expression of the remaining clock genes by SA or NH status. Our findings suggest that SA or related NH and clock gene expression may be interrelated. Future study of 24 h clock gene expression in SA is needed to establish the role of clock gene regulation on the pathway between SA and cardio-metabolic outcomes.

Keywords: circadian rhythm; clock genes; nocturnal hypoxemia; sleep apnea.

Conflict of interest statement

No conflicts of interest, financial or otherwise, are declared by the authors.

Figures

Fig. 1.

Percent difference in clock gene expression for those with sleep apnea (SA) (compared with those without sleep apnea). Data table below shows degree of percent difference for each clock gene, P value for statistical significance of that difference from the no SA group, and the sample size for each analysis. *P < 0.05.

Fig. 2.

Relative gene expression for sleep apnea in 4 categories of increasing severity.

Fig. 3.

Percent difference in clock gene expression for those with nocturnal hypoxemia (NH) (compared with those without NH). Data table below shows degree of percent difference for each clock gene, P value for statistical significance of that difference from the no NH group, and the sample size for each analysis. *P < 0.05.