Melatonin and oxidative DNA damage in REM- and NREM-related obstructive sleep apnea: an exploratory analysis of sleep-stage phenotypes.

PURPOSE: Obstructive sleep apnea is associated with intermittent hypoxia and oxidative stress. Whether oxidative and antioxidant biomarkers differ between rapid eye movement-related and non-rapid eye movement-related phenotypes remains unclear. We compared circulating melatonin and oxidative stress markers across sleep-stage phenotypes and disease severity categories.

METHODS

In this prospective case-control study, 165 participants (34 controls, 31 rapid eye movement-related obstructive sleep apnea, 100 non-rapid eye movement-related obstructive sleep apnea) underwent overnight polysomnography. Serum melatonin, 8-hydroxy-2'-deoxyguanosine, total oxidant status, and total antioxidant status were measured using enzyme-linked immunosorbent assay and colorimetric methods. The oxidative stress index was calculated as the ratio of total oxidant status to total antioxidant status multiplied by 100. Group comparisons were performed using nonparametric tests with appropriate post-hoc analyses. Additional analyses adjusted for age, body mass index, and sex using rank-transformed analysis of covariance. Correlations were evaluated using Spearman analysis with correction for multiple testing and formally compared between groups.

RESULTS

In unadjusted analyses, melatonin and 8-hydroxy-2'-deoxyguanosine levels were lower in obstructive sleep apnea, particularly in non-rapid eye movement-related and moderate disease. However, these differences were no longer statistically significant after adjustment for body mass index and sex. Total oxidant status, total antioxidant status, and oxidative stress index did not differ significantly between groups. Descriptive differences in correlation patterns were observed, but formal comparison showed no statistically significant between-phenotype differences.

CONCLUSION

Circulating redox biomarkers in obstructive sleep apnea show modest differences that appear largely influenced by body mass index and sex. These findings should be considered exploratory and hypothesis-generating rather than evidence of phenotype-specific biological mechanisms.