A missense variation in human casein kinase I epsilon gene that induces functional alteration and shows an inverse association with circadian rhythm sleep disorders

Atsuko Takano, Makoto Uchiyama, Naofumi Kajimura, Kazuo Mishima, Yuichi Inoue, Yuichi Kamei, Tsuyoshi Kitajima, Kayo Shibui, Masaaki Katoh, Tsuyoshi Watanabe, Yuki Hashimotodani, Toru Nakajima, Yuji Ozeki, Toru Hori, Naoto Yamada, Ryoichi Toyoshima, Norio Ozaki, Masako Okawa, Katsuya Nagai, Kiyohisa Takahashi & 3 others Yasushi Isojima, Toshio Yamauchi, Takashi Ebisawa

Research output: Contribution to journal › Article

85 Citations (Scopus)

Abstract

Recent studies have shown that functional variations in clock genes, which generate arcadian rhythms through interactive positive/ negative feedback loops, contribute to the development of circadian rhythm sleep disorders in humans. Another potential candidate for rhythm disorder susceptibility is casein kinase I epsilon (CKIε), which phosphorylates clock proteins and plays a pivotal role in the circadian clock. To determine whether variations in CKIε induce vulnerability to human circadian rhythm sleep disorders, such as delayed sleep phase syndrome (DSPS) and non-24-h sleep-wake syndrome (N-24), we analyzed all of the coding exons of the human CKIε gene. One of the variants identified encoded an amino-acid substitution S408N, eliminating one of the putative autophosphorylation sites in the carboxyl-terminal extension of CKIε. The N408 allele was less common in both DSPS (p = 0.028) and N-24 patients (p = 0.035) compared to controls. When DSPS and N-24 subjects were combined, based on an a priori prediction of a common mechanism underlying both DSPS and N-24, the inverse association between the N408 allele and rhythm disorders was highly significant (p = 0.0067, odds ratio = 0.42, 95% confidence interval: 0.22-0.79). In vitro kinase assay revealed that CKIε with the S408N variation was ∼ 1.8-fold more active than wild-type CKIε. These results indicate that the N408 allele in CKIε plays a protective role in the development of DSPS and N-24 through alteration of the enzyme activity.

Original languageEnglish
Pages (from-to)1901-1909
Number of pages9
JournalNeuropsychopharmacology
Volume29
Issue number10
DOIs
Publication statusPublished - 01-10-2004

Fingerprint

Circadian Rhythm Sleep Disorders
Casein Kinase I
Genes
Alleles
Circadian Clocks
Amino Acid Substitution
Exons
Sleep
Phosphotransferases
Odds Ratio
Confidence Intervals

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Psychiatry and Mental health

Cite this

Takano, Atsuko ; Uchiyama, Makoto ; Kajimura, Naofumi ; Mishima, Kazuo ; Inoue, Yuichi ; Kamei, Yuichi ; Kitajima, Tsuyoshi ; Shibui, Kayo ; Katoh, Masaaki ; Watanabe, Tsuyoshi ; Hashimotodani, Yuki ; Nakajima, Toru ; Ozeki, Yuji ; Hori, Toru ; Yamada, Naoto ; Toyoshima, Ryoichi ; Ozaki, Norio ; Okawa, Masako ; Nagai, Katsuya ; Takahashi, Kiyohisa ; Isojima, Yasushi ; Yamauchi, Toshio ; Ebisawa, Takashi. / A missense variation in human casein kinase I epsilon gene that induces functional alteration and shows an inverse association with circadian rhythm sleep disorders. In: Neuropsychopharmacology. 2004 ; Vol. 29, No. 10. pp. 1901-1909.
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abstract = "Recent studies have shown that functional variations in clock genes, which generate arcadian rhythms through interactive positive/ negative feedback loops, contribute to the development of circadian rhythm sleep disorders in humans. Another potential candidate for rhythm disorder susceptibility is casein kinase I epsilon (CKIε), which phosphorylates clock proteins and plays a pivotal role in the circadian clock. To determine whether variations in CKIε induce vulnerability to human circadian rhythm sleep disorders, such as delayed sleep phase syndrome (DSPS) and non-24-h sleep-wake syndrome (N-24), we analyzed all of the coding exons of the human CKIε gene. One of the variants identified encoded an amino-acid substitution S408N, eliminating one of the putative autophosphorylation sites in the carboxyl-terminal extension of CKIε. The N408 allele was less common in both DSPS (p = 0.028) and N-24 patients (p = 0.035) compared to controls. When DSPS and N-24 subjects were combined, based on an a priori prediction of a common mechanism underlying both DSPS and N-24, the inverse association between the N408 allele and rhythm disorders was highly significant (p = 0.0067, odds ratio = 0.42, 95{\%} confidence interval: 0.22-0.79). In vitro kinase assay revealed that CKIε with the S408N variation was ∼ 1.8-fold more active than wild-type CKIε. These results indicate that the N408 allele in CKIε plays a protective role in the development of DSPS and N-24 through alteration of the enzyme activity.",
author = "Atsuko Takano and Makoto Uchiyama and Naofumi Kajimura and Kazuo Mishima and Yuichi Inoue and Yuichi Kamei and Tsuyoshi Kitajima and Kayo Shibui and Masaaki Katoh and Tsuyoshi Watanabe and Yuki Hashimotodani and Toru Nakajima and Yuji Ozeki and Toru Hori and Naoto Yamada and Ryoichi Toyoshima and Norio Ozaki and Masako Okawa and Katsuya Nagai and Kiyohisa Takahashi and Yasushi Isojima and Toshio Yamauchi and Takashi Ebisawa",
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Takano, A, Uchiyama, M, Kajimura, N, Mishima, K, Inoue, Y, Kamei, Y, Kitajima, T, Shibui, K, Katoh, M, Watanabe, T, Hashimotodani, Y, Nakajima, T, Ozeki, Y, Hori, T, Yamada, N, Toyoshima, R, Ozaki, N, Okawa, M, Nagai, K, Takahashi, K, Isojima, Y, Yamauchi, T & Ebisawa, T 2004, 'A missense variation in human casein kinase I epsilon gene that induces functional alteration and shows an inverse association with circadian rhythm sleep disorders', Neuropsychopharmacology, vol. 29, no. 10, pp. 1901-1909. https://doi.org/10.1038/sj.npp.1300503

A missense variation in human casein kinase I epsilon gene that induces functional alteration and shows an inverse association with circadian rhythm sleep disorders. / Takano, Atsuko; Uchiyama, Makoto; Kajimura, Naofumi; Mishima, Kazuo; Inoue, Yuichi; Kamei, Yuichi; Kitajima, Tsuyoshi; Shibui, Kayo; Katoh, Masaaki; Watanabe, Tsuyoshi; Hashimotodani, Yuki; Nakajima, Toru; Ozeki, Yuji; Hori, Toru; Yamada, Naoto; Toyoshima, Ryoichi; Ozaki, Norio; Okawa, Masako; Nagai, Katsuya; Takahashi, Kiyohisa; Isojima, Yasushi; Yamauchi, Toshio; Ebisawa, Takashi.

In: Neuropsychopharmacology, Vol. 29, No. 10, 01.10.2004, p. 1901-1909.

Research output: Contribution to journal › Article

TY - JOUR

T1 - A missense variation in human casein kinase I epsilon gene that induces functional alteration and shows an inverse association with circadian rhythm sleep disorders

AU - Takano, Atsuko

AU - Uchiyama, Makoto

AU - Kajimura, Naofumi

AU - Mishima, Kazuo

AU - Inoue, Yuichi

AU - Kamei, Yuichi

AU - Kitajima, Tsuyoshi

AU - Shibui, Kayo

AU - Katoh, Masaaki

AU - Watanabe, Tsuyoshi

AU - Hashimotodani, Yuki

AU - Nakajima, Toru

AU - Ozeki, Yuji

AU - Hori, Toru

AU - Yamada, Naoto

AU - Toyoshima, Ryoichi

AU - Ozaki, Norio

AU - Okawa, Masako

AU - Nagai, Katsuya

AU - Takahashi, Kiyohisa

AU - Isojima, Yasushi

AU - Yamauchi, Toshio

AU - Ebisawa, Takashi

PY - 2004/10/1

Y1 - 2004/10/1

N2 - Recent studies have shown that functional variations in clock genes, which generate arcadian rhythms through interactive positive/ negative feedback loops, contribute to the development of circadian rhythm sleep disorders in humans. Another potential candidate for rhythm disorder susceptibility is casein kinase I epsilon (CKIε), which phosphorylates clock proteins and plays a pivotal role in the circadian clock. To determine whether variations in CKIε induce vulnerability to human circadian rhythm sleep disorders, such as delayed sleep phase syndrome (DSPS) and non-24-h sleep-wake syndrome (N-24), we analyzed all of the coding exons of the human CKIε gene. One of the variants identified encoded an amino-acid substitution S408N, eliminating one of the putative autophosphorylation sites in the carboxyl-terminal extension of CKIε. The N408 allele was less common in both DSPS (p = 0.028) and N-24 patients (p = 0.035) compared to controls. When DSPS and N-24 subjects were combined, based on an a priori prediction of a common mechanism underlying both DSPS and N-24, the inverse association between the N408 allele and rhythm disorders was highly significant (p = 0.0067, odds ratio = 0.42, 95% confidence interval: 0.22-0.79). In vitro kinase assay revealed that CKIε with the S408N variation was ∼ 1.8-fold more active than wild-type CKIε. These results indicate that the N408 allele in CKIε plays a protective role in the development of DSPS and N-24 through alteration of the enzyme activity.

AB - Recent studies have shown that functional variations in clock genes, which generate arcadian rhythms through interactive positive/ negative feedback loops, contribute to the development of circadian rhythm sleep disorders in humans. Another potential candidate for rhythm disorder susceptibility is casein kinase I epsilon (CKIε), which phosphorylates clock proteins and plays a pivotal role in the circadian clock. To determine whether variations in CKIε induce vulnerability to human circadian rhythm sleep disorders, such as delayed sleep phase syndrome (DSPS) and non-24-h sleep-wake syndrome (N-24), we analyzed all of the coding exons of the human CKIε gene. One of the variants identified encoded an amino-acid substitution S408N, eliminating one of the putative autophosphorylation sites in the carboxyl-terminal extension of CKIε. The N408 allele was less common in both DSPS (p = 0.028) and N-24 patients (p = 0.035) compared to controls. When DSPS and N-24 subjects were combined, based on an a priori prediction of a common mechanism underlying both DSPS and N-24, the inverse association between the N408 allele and rhythm disorders was highly significant (p = 0.0067, odds ratio = 0.42, 95% confidence interval: 0.22-0.79). In vitro kinase assay revealed that CKIε with the S408N variation was ∼ 1.8-fold more active than wild-type CKIε. These results indicate that the N408 allele in CKIε plays a protective role in the development of DSPS and N-24 through alteration of the enzyme activity.

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Takano A, Uchiyama M, Kajimura N, Mishima K, Inoue Y, Kamei Y et al. A missense variation in human casein kinase I epsilon gene that induces functional alteration and shows an inverse association with circadian rhythm sleep disorders. Neuropsychopharmacology. 2004 Oct 1;29(10):1901-1909. https://doi.org/10.1038/sj.npp.1300503

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