|
 |
|
|
|
EMBO reports 2, 4, 342–346 (2001)
doi:10.1093/embo-reports/kve070
Published online: April 2001
Association of structural polymorphisms in the human period3 gene with delayed sleep phase syndrome
Takashi Ebisawa1, Makoto Uchiyama2, Naofumi Kajimura3, Kazuo Mishima4, Yuichi Kamei5, Masaaki Katoh3, Tsuyoshi Watanabe3, Masanori Sekimoto3, Kayo Shibui2, Keiko Kim6, Yoshinao Kudo5, Yuji Ozeki7, Mariko Sugishita1, Ryoichi Toyoshima1, Yuichi Inoue8, Naoto Yamada7, Takahiro Nagase9, Norio Ozaki10, Osamu Ohara9, Norio Ishida11, Masako Okawa7, Kiyohisa Takahashi3, 5 & Toshio Yamauchi1
|
|
|
|
1 Department of Psychiatry, Saitama Medical School, 38 Morohongo, Saitama 350-0495, Japan
2 Department of Psychophysiology, National Center of Neurology and Psychiatry (NCNP), 1-7-3 Kohnodai, Chiba 272-0827, Japan
3 Musashi Hospital, NCNP, 4-1-1 Ogawa-cho, Tokyo 187-0031, Japan
4 Department of Psychiatry, Akita University School of Medicine, 1-1-1 Hondo, Akita 010-8543, Japan
5 Kohnodai Hospital, NCNP, 1-7-1 Kohnodai, Chiba 272-0827, Japan
6 Department of Psychiatry, Tokyo Women's Medical College, 8-1 Kawata-cho, Tokyo 162-8666, Japan
7 Department of Psychiatry, Shiga University of Medical Science, Seta Tsukinowa-cho, Shiga 520-2192, Japan
8 Department of Psychiatry, Juntendo University, School of Medicine, 2-1-1 Hongo, Tokyo 113-8431, Japan
9 Kazusa DNA Research Institute, 1532-3 Yana, Chiba 292-0812, Japan
10 Department of Psychiatry, Fujita Health University School of Medicine, Machida Rakugabuchi, Aichi 470-1192 Japan
11 National Institute of Bioscience and Human Technology, Agency of Industrial Science and Technology, 1-1 Higashi, Ibaraki 305-8566, Japan
To whom correspondence should be addressed
Takashi Ebisawa Tel: +81 492 76 1213; Fax: +81 492 76 1622; tebisawa@saitama-med.ac.jp
Received 23 November 2000; Accepted 12 February 2001.
|
|
|
|
Abstract
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.
|
|
top  |
|
|
|
