Association of structural polymorphisms in the human period3 gene with delayed sleep phase syndrome.
Recent progress in biological clock research has facilitated genetic analysis of circadian rhythm sleep disorders, such as delayed sleep phase syndrome (DSPS) and non-24-h sleep-wake syndrome (N-24). We analyzed the human period3 (hPer3) gene, one of the human homologs of the Drosophila clock-gene period (Per), as a possible candidate for rhythm disorder susceptibility. All of the coding exons in the hPer3 gene were screened for polymorphisms by a PCR-based strategy using genomic DNA samples from sleep disorder patients and control subjects. We identified six sequence variations with amino acid changes, of which five were common and predicted four haplotypes of the hPer3 gene. One of the haplotypes was significantly associated with DSPS (Bonferroni's corrected P = 0.037; odds ratio = 7.79; 95% CI 1.59-38.3) in our study population. Our results suggest that structural polymorphisms in the hPer3 gene may be implicated in the pathogenesis of DSPS.
Ebisawa
T
T
Department of Psychiatry, Saitama Medical School, 38 Morohongo, Saitama 350-0495, Japan. tebisawa@saitama-med.ac.jp
Uchiyama
M
M
Kajimura
N
N
Mishima
K
K
Kamei
Y
Y
Katoh
M
M
Watanabe
T
T
Sekimoto
M
M
Shibui
K
K
Kim
K
K
Kudo
Y
Y
Ozeki
Y
Y
Sugishita
M
M
Toyoshima
R
R
Inoue
Y
Y
Yamada
N
N
Nagase
T
T
Ozaki
N
N
Ohara
O
O
Ishida
N
N
Okawa
M
M
Takahashi
K
K
Yamauchi
T
T
D000293:Adolescent; D000328:Adult; D000483:Alleles; D000595:Amino Acid Sequence; D001483:Base Sequence; D016022:Case-Control Studies; D002940:Circadian Rhythm; D018076:DNA, Complementary / Q000378:metabolism; D029721:Drosophila Proteins; D005091:Exons; D005260:Female; D015723:Gene Library; D006239:Haplotypes; D006579:Heterozygote; D006801:Humans; D007438:Introns; D008297:Male; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics*; D016017:Odds Ratio; D056950:Period Circadian Proteins; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D018807:Polymorphism, Single-Stranded Conformational; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid; D020178:Sleep Disorders, Circadian Rhythm / Q000235:genetics*; D014157:Transcription Factors
D018076:DNA, Complementary; D029721:Drosophila Proteins; D009687:Nuclear Proteins; C539040:PER protein, Drosophila; C512644:PER3 protein, human; D056950:Period Circadian Proteins; D014157:Transcription Factors