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J Clin Endocrinol Metab. 2012 Mar;97(3):E433-7. doi: 10.1210/jc.2011-2391. Epub 2011 Dec 21.

Human melatonin and alerting response to blue-enriched light depend on a polymorphism in the clock gene PER3.

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Centre for Chronobiology, Psychiatric Hospital of the University of Basel, Wilhelm Kleinstrasse 27, CH-4012 Basel, Switzerland.



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.


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.


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.


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).


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.

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