Diurnal preference, mood and the response to morning light in relation to polymorphisms in the human clock gene PER3

PER3 gene polymorphisms have been associated with differences in human sleep-wake phenotypes, and sensitivity to light. The aims of this study were to assess: i) the frequency of allelic variants at two PER3 polymorphic sites (rs57875989 length polymorphism: PER3 (4), PER3 (5); rs228697 SNP: PER3 (C), PER3 (G)) in relation to sleep-wake timing; ii) the effect of morning light on behavioural/circadian variables in PER3 (4) /PER3 (4) and PER3 (5) /PER3 (5) homozygotes. 786 Caucasian subjects living in Northern Italy donated buccal DNA and completed diurnal preference, sleep quality/timing and sleepiness/mood questionnaires. 19 PER3 (4) /PER3 (4) and 11 PER3 (5) /PER3 (5) homozygotes underwent morning light administration, whilst monitoring sleep-wake patterns and the urinary 6-sulphatoxymelatonin (aMT6s) rhythm. No significant relationship was observed between the length polymorphism and diurnal preference. By contrast, a significant association was observed between the PER3 (G) variant and morningness (OR = 2.10), and between the PER3 (G)-PER3 (4) haplotype and morningness (OR = 2.19), for which a mechanistic hypothesis is suggested. No significant differences were observed in sleep timing/aMT6s rhythms between PER3 (5) /PER3 (5) and PER3 (4) /PER3 (4) subjects at baseline. After light administration, PER3 (4) /PER3 (4) subjects advanced their aMT6s acrophase (p < 0.05), and showed a trend of advanced sleep-wake timing. In conclusion, significant associations were observed between PER3 polymorphic variants/their combinations and both diurnal preference and the response to light.