title: Human melatonin and alerting response to blue-enriched light depend on a polymorphism in the clock gene PER3.
abstract: BACKGROUND
  Light exposure, particularly at the short-wavelength range, triggers several nonvisual responses in humans. However, the extent to which the melatonin-suppressing and alerting effect of light differs among individuals remains unknown.
  
  
  OBJECTIVE
  Here we investigated whether blue-enriched polychromatic light impacts differentially on melatonin and subjective and objective alertness in healthy participants genotyped for the PERIOD3 (PER3) variable-number, tandem-repeat polymorphism.
  
  
  METHODS
  Eighteen healthy young men homozygous for the PER3 polymorphism (PER3(5/5)and PER3(4/4)) underwent a balanced crossover design during the winter season, with light exposure to compact fluorescent lamps of 40 lux at 6500 K and at 2500 K during 2 h in the evening.
  
  
  RESULTS
  In comparison to light at 2500 K, blue-enriched light at 6500 K induced a significant suppression of the evening rise in endogenous melatonin levels in PER3(5/5) individuals but not in PER3(4/4). Likewise, PER3(5/5) individuals exhibited a more pronounced alerting response to light at 6500 K than PER3(4/4) volunteers. Waking electroencephalographic activity in the theta range (5-7 Hz), a putative correlate of sleepiness, was drastically attenuated during light exposure at 6500 K in PER3(5/5) individuals as compared with PER3(4/4).
  
  
  CONCLUSIONS
  We provide first evidence that humans homozygous for the PER3 5/5 allele are particularly sensitive to blue-enriched light, as indexed by the suppression of endogenous melatonin and waking theta activity. Light sensitivity in humans may be modulated by a clock gene polymorphism implicated in the sleep-wake regulation.
authors.affiliation: Centre for Chronobiology, Psychiatric Hospital of the University of Basel, Wilhelm Kleinstrasse 27, CH-4012 Basel, Switzerland.
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Chellappa
authors.forename: Antoine U
authors.initials: AU
authors.lastname: Viola
authors.forename: Christina
authors.initials: C
authors.lastname: Schmidt
authors.forename: Valérie
authors.initials: V
authors.lastname: Bachmann
authors.forename: Virginie
authors.initials: V
authors.lastname: Gabel
authors.forename: Micheline
authors.initials: M
authors.lastname: Maire
authors.forename: Carolin F
authors.initials: CF
authors.lastname: Reichert
authors.forename: Amandine
authors.initials: A
authors.lastname: Valomon
authors.forename: Thomas
authors.initials: T
authors.lastname: Götz
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Landolt
authors.forename: Christian
authors.initials: C
authors.lastname: Cajochen
mesh_terms: D000328:Adult; D000483:Alleles; D018592:Cross-Over Studies; D005260:Female; D005838:Genotype; D006720:Homozygote; D006801:Humans; D008027:Light; D008297:Male; D008550:Melatonin / Q000097:blood* / Q000235:genetics; D018598:Minisatellite Repeats; D056950:Period Circadian Proteins / Q000235:genetics*; D011110:Polymorphism, Genetic; D012890:Sleep / Q000235:genetics; D011795:Surveys and Questionnaires; D014851:Wakefulness / Q000235:genetics*
chemical_list: C512644:PER3 protein, human; D056950:Period Circadian Proteins; D008550:Melatonin