title: The 3111T/C polymorphism of hClock is associated with evening preference and delayed sleep timing in a Japanese population sample.
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.
authors.affiliation: Division of Neuropsychiatry, Department of Neuro and Locomotor Science, Akita University School of Medicine, Akita, Japan. mishima@psy.med.akita-u.ac.jp
authors.forename: Kazuo
authors.initials: K
authors.lastname: Mishima
authors.forename: Takuma
authors.initials: T
authors.lastname: Tozawa
authors.forename: Kohtoku
authors.initials: K
authors.lastname: Satoh
authors.forename: Hidetomo
authors.initials: H
authors.lastname: Saitoh
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Mishima
mesh_terms: D000328:Adult; D000483:Alleles; D056926:CLOCK Proteins; D002940:Circadian Rhythm / Q000502:physiology*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007564:Japan; D008297:Male; D020641:Polymorphism, Single Nucleotide; D012890:Sleep / Q000235:genetics* / Q000502:physiology; D013997:Time Factors; D015534:Trans-Activators / Q000235:genetics*
chemical_list: D015534:Trans-Activators; D056926:CLOCK Proteins; C538943:CLOCK protein, human