Human Melatonin and Alerting Response to Blue-Enriched Light Depend on a Polymorphism in the Clock Gene PER3

Dec 23, 2011The Journal of clinical endocrinology and metabolism

Melatonin and alertness responses to blue light vary with a common PER3 gene variation

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Abstract

Blue-enriched light at 6500 K suppressed melatonin levels significantly in PER3(5/5) individuals compared to those with the PER3(4/4) genotype.

Individuals with the PER3(5/5) genotype experienced a greater suppression of evening melatonin levels when exposed to blue-enriched light.
The alertness response to 6500 K light was more pronounced in PER3(5/5) participants than in those with the PER3(4/4) genotype.
Waking brain activity associated with sleepiness was significantly reduced during exposure to 6500 K light in PER3(5/5) individuals compared to PER3(4/4).
Results suggest that sensitivity to blue-enriched light may vary based on genetic differences in the PERIOD3 gene.

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CONTEXT: 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.

DESIGN, SETTING, AND PARTICIPANTS: 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.

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Human Melatonin and Alerting Response to Blue-Enriched Light Depend on a Polymorphism in the Clock Gene PER3

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