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Association of structural polymorphisms in the human period3 gene with delayed sleep phase syndrome
Author(s) -
Ebisawa Takashi,
Uchiyama Makoto,
Kajimura Naofumi,
Mishima Kazuo,
Kamei Yuichi,
Katoh Masaaki,
Watanabe Tsuyoshi,
Sekimoto Masanori,
Shibui Kayo,
Kim Keiko,
Kudo Yoshinao,
Ozeki Yuji,
Sugishita Mariko,
Toyoshima Ryoichi,
Inoue Yuichi,
Yamada Naoto,
Nagase Takahiro,
Ozaki Norio,
Ohara Osamu,
Ishida Norio,
Okawa Masako,
Takahashi Kiyohisa,
Yamauchi Toshio
Publication year - 2001
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.1093/embo-reports/kve070
Subject(s) - haplotype , genetics , biology , circadian rhythm , gene , exon , clock , candidate gene , bonferroni correction , genotype , circadian clock , endocrinology , statistics , mathematics
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.