Mutation screening of the human Clock gene in circadian rhythm sleep disorders.
We tested whether the human Clock (hClock) gene, one of the essential components of the circadian oscillator, is implicated in the vulnerability to delayed sleep phase syndrome (DSPS) and non-24-hour sleep-wake syndrome (N-24). Screening in the entire coding region of the hClock gene with PCR amplification revealed three polymorphisms, of which two predicted the amino acid substitutions R533Q and H542R. The frequencies of the R533Q and H542R alleles in patients with DSPS or N-24 were very low and not significantly different from those in control subjects. A T3111C polymorphism in the 3'-untranslated region of hClock, which had been reportedly associated with morning or evening preference for activity, was also investigated; the results showed that the 3111C allele frequency decreased in DSPS. Polymorphisms in the coding region of the hClock gene are unlikely to play an important role in the development of DSPS or N-24. The possible contribution of the T3111C polymorphism to DSPS susceptibility should be studied further.
Iwase
Toshio
T
Department of Neuropsychiatry, Saitama Medical School, 38 Morohongo, Moroyama-cho, Iruma-gun, 350-0495, Japan.
Kajimura
Naofumi
N
Uchiyama
Makoto
M
Ebisawa
Takashi
T
Yoshimura
Kimio
K
Kamei
Yuichi
Y
Shibui
Kayo
K
Kim
Keiko
K
Kudo
Yoshinao
Y
Katoh
Masaaki
M
Watanabe
Tsuyoshi
T
Nakajima
Toru
T
Ozeki
Yuji
Y
Sugishita
Mariko
M
Hori
Toru
T
Ikeda
Masaaki
M
Toyoshima
Ryoichi
R
Inoue
Yuichi
Y
Yamada
Naoto
N
Mishima
Kazuo
K
Nomura
Masahiko
M
Ozaki
Norio
N
Okawa
Masako
M
Takahashi
Kiyohisa
K
Yamauchi
Toshio
T
D000328:Adult; D000483:Alleles; D056926:CLOCK Proteins; D002940:Circadian Rhythm / Q000235:genetics; D005260:Female; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics; D018807:Polymorphism, Single-Stranded Conformational; D020178:Sleep Disorders, Circadian Rhythm / Q000235:genetics*; D015534:Trans-Activators / Q000235:genetics*
D015534:Trans-Activators; D056926:CLOCK Proteins; C538943:CLOCK protein, human