title: Is Period3 Genotype Associated With Sleep and Recovery in Patients With Disorders of Consciousness?
abstract: Background Sleep evaluation is increasingly being used as prognostic tool in patients with disorders of consciousness, but, surprisingly, the role of Period3 (Per3) gene polymorphism has never been evaluated. Objective The aim of this study was to investigate the contribution of Per3 genotype on sleep quantity and consciousness recovery level in patients with disorders of consciousness (DOC). Methods In this observational study, we evaluated 71 patients with DOC classified as vegetative state/unresponsive wakefulness syndrome or minimally conscious state. Demographic and clinical data were collected and a standardised diagnostic workup, including a polysomnographic record, was applied. After informed consent provided by proxy, genomic DNA was obtained and Per3 polymorphism was analysed by polymerase chain reaction to identify 5/5, 4/5, or 4/4 genotype. Results Per3(5/5) genotype was found in 12.7% of our DOC patients. The median total Coma Recovery Scale-revised score in Per3(5/5) carriers was significantly higher than 4/4 genotype (10, range 5-16 vs 7, range 4-11; post hoc P = .036). Moreover, total sleep time seemed to be higher in 5/5 genotype (5/5, 221 minutes, range 88-515 minutes; 4/4, 151.5 minutes, range 36-477 minutes; and 4/5, 188 minutes, range 44-422 minutes). Conclusion For the first time we have shown a possible association between Per3 polymorphism and consciousness recovery level in DOC patients. Even though the exact molecular mechanism has not been defined, we speculate that its effect is mediated by higher total sleep time and slow wave sleep, which would improve the preservation of main cerebral connections.
authors.affiliation: Neurological Institute "C. Besta" IRCCS Foundation, Milan, Italy gloria.bedini@istituto-besta.it.
authors.forename: Gloria
authors.initials: G
authors.lastname: Bedini
authors.affiliation: Neurological Institute "C. Besta" IRCCS Foundation, Milan, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Bersano
authors.affiliation: Neurological Institute "C. Besta" IRCCS Foundation, Milan, Italy.
authors.forename: Davide Rossi
authors.initials: DR
authors.lastname: Sebastiano
authors.affiliation: Neurological Institute "C. Besta" IRCCS Foundation, Milan, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Sattin
authors.affiliation: Neurological Institute "C. Besta" IRCCS Foundation, Milan, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Ciaraffa
authors.affiliation: Neurological Institute "C. Besta" IRCCS Foundation, Milan, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Tosetti
authors.affiliation: Neurological Institute "C. Besta" IRCCS Foundation, Milan, Italy.
authors.forename: Greta
authors.initials: G
authors.lastname: Brenna
authors.affiliation: Neurological Institute "C. Besta" IRCCS Foundation, Milan, Italy.
authors.forename: Silvana
authors.initials: S
authors.lastname: Franceschetti
authors.affiliation: Neurological Institute "C. Besta" IRCCS Foundation, Milan, Italy.
authors.forename: Emilio
authors.initials: E
authors.lastname: Ciusani
authors.affiliation: Neurological Institute "C. Besta" IRCCS Foundation, Milan, Italy.
authors.forename: Matilde
authors.initials: M
authors.lastname: Leonardi
authors.affiliation: Neurological Institute "C. Besta" IRCCS Foundation, Milan, Italy.
authors.forename: Jesus
authors.initials: J
authors.lastname: Vela-Gomez
authors.affiliation: Neurological Institute "C. Besta" IRCCS Foundation, Milan, Italy.
authors.forename: Giorgio B
authors.initials: GB
authors.lastname: Boncoraglio
authors.affiliation: Neurological Institute "C. Besta" IRCCS Foundation, Milan, Italy.
authors.forename: Eugenio A
authors.initials: EA
authors.lastname: Parati
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016009:Chi-Square Distribution; D003244:Consciousness Disorders / Q000235:genetics* / Q000503:physiopathology*; D004569:Electroencephalography; D005071:Evoked Potentials / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D018598:Minisatellite Repeats / Q000235:genetics; D056950:Period Circadian Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D017286:Polysomnography; D020127:Recovery of Function / Q000235:genetics*; D012189:Retrospective Studies; D012890:Sleep / Q000235:genetics*; D055815:Young Adult
chemical_list: C512644:PER3 protein, human; D056950:Period Circadian Proteins
keywords: Period3 gene; disorders of consciousness; minimally conscious state; outcome research; sleep; vegetative state/unresponsive wakefulness syndrome