PERIOD3 polymorphism predicts sleepiness and circadian phase in night workers.
Drake-C; Howard-R; Levin-A; Roth-T; Gumenyuk-V
Sleep 2013 Jun; 36(Abstract Suppl):A181
Introduction: A likely functional variable number tandem repeat (VNTR) polymorphism in the PERIOD3 (PER3) gene has been shown to be associated with sleepiness and circadian phase. This study attempted to determine nocturnal sleepiness levels among night workers differing by PER3 genotype, and whether this difference is associated with differences in circadian phase. Methods: 24 subjects (age: 35+/-8.9 years, 19F) working 10-12 hour shifts between 1900 and 0800 participated in a 25 hour protocol, during which they were kept awake in dim light (< 10 lux) with salivary melatonin assays every 30 minutes to determine dim light melatonin onset (DLMO). A nocturnal multiple sleep latency test (MSLT) was done at 2230, 0030, 0230, and 0430. The two alleles at the PER3 VNTR correspond to 4 and 5 repeats, and each subject's genotype [11 PER3(4/4), 12 PER3(4/5),and 1 PER3(5/5)] was determined from DNA derived from a saliva sample. Due to the small sample of PER3(5/5) individuals, a dominant genetic model [PER3(4/4) in comparison to carriers of the 5-repeat allele, PER3(-/5) was applied in all analysis of variance models. Results: There were significant differences between PER3(-/5) and PER3(4/4) genotype classes for the MSLT (3.52+/-3.44min vs.10.39+/-641 min, p=0.006), Epworth Sleepiness Scale (ESS) score (12.08+/-2.55 vs. 8.00+/-1.94, p<0.001), and DLMO (2044+/-6.61hrs vs. 0246+/-4.97hrs, p=0.02). Importantly, differences in MSLT score (p=0.02) and ESS score (p=0.004) remained significant after controlling for DLMO, suggesting that sleepiness between genotypes is, at least in part, independent of circadian phase. Conclusion: Carriers of at least one PER3 5-repeat allele [PER3(-/5)] were significantly sleepier and had a considerably earlier (approximately 6hrs) circadian phase compared with PER3(4/4) individuals. These differences found between genotype classes in a common genetic variant warrant additional studies to assess the clinical significance of the PER3 VNTR in shift worker morbidity.
Sleep-deprivation; Sleep-disorders; Shift-work; Shift-workers; Circadian-rhythms; Work-intervals; Humans; Physiological-response; Biological-rhythms; Biomarkers; Morphology; Genes; Genetic-factors; Age-groups; Bioassays; Physiological-testing; Deoxyribonucleic-acids; Models; Analytical-models; Analytical-processes
C. Drake, Sleep Disorders and Research Center, Henry Ford Hospital, Detroit, MI, USA
Henry Ford Health System, Detroit, Michigan