title: Length polymorphism in the Period 3 gene is associated with sleepiness and maladaptive circadian phase in night-shift workers.
abstract: The objective of the current study was to determine if night-shift workers carrying the five-repeat variant of the Period 3 gene show elevated levels of nocturnal sleepiness and earlier circadian phase compared with homozygotes for the four-repeat allele. Twenty-four permanent night-shift workers were randomly selected from a larger study. Participants took part in an observational laboratory protocol including an overnight multiple sleep latency test and half-hourly saliva collection for calculation of dim-light melatonin onset. Period 3(-/5) shift workers had significantly lower multiple sleep latency test during overnight work hours compared with Period 3(4/4) workers (3.52 ± 23.44 min versus 10.39 ± 6.41 min, P = 0.003). We observed no significant difference in sleepiness during early morning hours following acute sleep deprivation. Long-allele carriers indicated significantly higher sleepiness on the Epworth Sleepiness Scale administered at 17:00 hours (12.08 ± 2.55 versus 8.00 ± 1.94, P < 0.001). We observed a significantly earlier melatonin onset in Period 3(-/5) individuals compared with Period 3(4/4) shift workers (20:44 ± 6:37 versus 02:46 ± 4:58, P = 0.021). Regression analysis suggests that Period 3 genotype independently predicts sleepiness even after controlling for variations in circadian phase, but we were unable to link Period 3 to circadian phase when controlling for sleepiness. Period 3(-/5) shift workers showed both subjective and objective sleepiness in the pathological range, while their Period 3(4/4) counterparts showed sleepiness within normal limits. Period 3(-/5) night workers also show a mean circadian phase 6 h earlier (i.e. less adapted) than Period 3(4/4) workers. Because Period 3(-/5) workers have maladaptive circadian phase as well as pathological levels of sleepiness, they may be at greater risk for occupational and automotive accidents. We interpret these findings as a call for future research on the role of Period 3 in sleepiness and circadian phase, especially as they relate to night work.
authors.affiliation: Sleep Disorders and Research Center, Henry Ford Hospital, Detroit, MI, USA.
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Drake
authors.affiliation: Sleep Disorders and Research Center, Henry Ford Hospital, Detroit, MI, USA.|Pritzker School of Medicine, University of Chicago, Chicago, IL, USA.
authors.forename: Ren
authors.initials: R
authors.lastname: Belcher
authors.affiliation: Sleep Disorders and Research Center, Henry Ford Hospital, Detroit, MI, USA.|University of Michigan Medical School, Ann Arbor, MI, USA.
authors.forename: Ryan
authors.initials: R
authors.lastname: Howard
authors.affiliation: Sleep Disorders and Research Center, Henry Ford Hospital, Detroit, MI, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Roth
authors.affiliation: Department of Public Health Sciences, Henry Ford Hospital, Detroit, MI, USA.
authors.forename: Albert M
authors.initials: AM
authors.lastname: Levin
authors.affiliation: Sleep Disorders and Research Center, Henry Ford Hospital, Detroit, MI, USA.|Magnetoencephalography Laboratory, Meadowlands Hospital, Secaucus, NJ, USA.
authors.forename: Valentina
authors.initials: V
authors.lastname: Gumenyuk
mesh_terms: D000328:Adult; D000483:Alleles; D016022:Case-Control Studies; D002940:Circadian Rhythm / Q000235:genetics* / Q000528:radiation effects; D005260:Female; D006801:Humans; D008027:Light; D008297:Male; D008550:Melatonin / Q000032:analysis; D056950:Period Circadian Proteins / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D017286:Polysomnography; D012463:Saliva / Q000737:chemistry; D012890:Sleep; D012892:Sleep Deprivation / Q000235:genetics / Q000503:physiopathology; D020178:Sleep Disorders, Circadian Rhythm / Q000235:genetics* / Q000503:physiopathology; D012894:Sleep Stages / Q000235:genetics* / Q000528:radiation effects; D013997:Time Factors
chemical_list: C512644:PER3 protein, human; D056950:Period Circadian Proteins; D008550:Melatonin
keywords: DLMO; Fatigue; MSLT; PER 3; circadian rhythms; shift work disorder