The 3111T/C polymorphism of hClock is associated with evening preference and delayed sleep timing in a Japanese population sample

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Abstract
Sleep timing is influenced by the circadian system. Morningness‐eveningness (ME) preference in humans is affected by the free‐running period, which is determined by circadian clock‐relevant genes. In this study, we investigated association between the 3111T/C polymorphism in the 3′‐flanking region of hClock (Homo sapiens Clock homolog) and ME preference in 421 Japanese subjects. The Horne–Ostberg ME questionnaire (MEQ) scores showed normal distribution, with mean score of 51.2 ± 1.4 (range, 25–73), and scores were positively correlated with sleep onset time (r = 0.541, P < 0.001) and wake time (r = 0.513, P < 0.001). MEQ scores were significantly lower in subjects with 3111C/C (n = 12) than in subjects with 3111T/C (n = 106, P < 0.001) or 3111T/T (n = 303, P < 0.001), suggesting a stronger eveningness preference in 3111C/C homozygotes. This group also showed significantly delayed sleep onset (P < 0.001), shorter sleep time (P < 0.001), and greater daytime sleepiness (P < 0.001) in comparison to parameters in the subjects with the 3111T allele. There was no significant difference in any of these parameters between the 3111C/T and 3111T/T genotypes. The influence of the 3111T/C polymorphism on ME preferences in Caucasian populations remains controversial. The present findings in a Japanese population sample, which should have a relatively low risk of population stratification effects, suggest the significance of the association of the 3111C/C allele of hClock with evening preference.

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