Mutation screening of the human Clock gene in circadian rhythm sleep disorders

Iwase, Toshio; Kajimura, Naofumi; Uchiyama, Makoto; Ebisawa, Takashi; Yoshimura, Kimio; Kamei, Yuichi; Shibui, Kayo; Kim, Keiko; Kudo, Yoshinao; Katoh, Masaaki; Watanabe, Takehiko; Nakajima, Toru; Ozeki, Yuji; Sugishita, Mariko; Hori, Toru; Ikeda, Masaaki; Toyoshima, Ryoichi; Inoue, Yuichi; Yamada, Naoto; Mishima, Kazuo; Nomura, Masahiko; Ozaki, Norio; Okawa, Masako; Takahashi, Keiichi; Yamauchi, Takeshi

doi:10.1016/s0165-1781(02)00006-9

Cited by 130 publications

(63 citation statements)

References 20 publications

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“…17 Although we did not perform any assessment of sleep patterns in our subjects, it is of interest that the rs1801260 polymorphism has previously been associated with sleep dysregulation in humans in many [31][32][33][34][35][36][37][38] but not all studies. 39 These findings, together with the present results may provide genetic evidence to support epidemiological studies associating sleep disturbance with the development of diabetes and obesity.…”

Section: Discussionmentioning

confidence: 99%

Association between polymorphisms in the Clock gene, obesity and the metabolic syndrome in man

2007

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Objective: Accumulating evidence raises the hypothesis that dysregulation of intrinsic clock mechanisms are involved in the development of the metabolic syndrome, type 2 diabetes mellitus and cardiovascular disease. The aim of the present study was to investigate the relationship between three known common polymorphisms in the Clock gene and features of the metabolic syndrome in man. Methods: Genotype and haplotype analysis was carried out in a cohort of 537 individuals from 89 families characterized for inflammatory, atherothrombotic and metabolic risk associated with insulin resistance. Results: Heritability of the metabolic syndrome, defined according to International Diabetes Federation criteria, was 0.40. Haplotype analysis indicated three common haplotypes: CAT, TGT and CGC (rs4864548-rs3736544-rs1801260) with frequencies of 31, 33 and 28%, respectively. The CGC haplotype was less prevalent in subjects with the metabolic syndrome (P ¼ 0.0015) and was associated with lower waist circumference (P ¼ 0.007), lower hip circumference (P ¼ 0.023), lower body mass index (P ¼ 0.043) and lower leptin levels (P ¼ 0.028). The CAT haplotype was significantly associated with the presence of the metabolic syndrome (P ¼ 0.020). Conclusions: These findings suggest that the Clock gene CGC haplotype may be protective for the development of obesity and support the hypothesis that genetic variation in the Clock gene may play a role in the development of the metabolic syndrome, type 2 diabetes and cardiovascular disease.

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Section: Discussionmentioning

confidence: 99%

Association between polymorphisms in the Clock gene, obesity and the metabolic syndrome in man

2007

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“…Even individuals that are genetically predisposed towards "eveningness" (a preference for the evening) versus "morningness" (a preference for the morning) are more likely to develop depression (Drennan et al, 1991;Chelminski et al, 1999). Genetic variations in the circadian genes have been found to associate with these sleep disorders and diurnal preference measures including an association between certain variants of Per2, and CK1δ with FASPS; Per3, CLOCK, and CK1ε with DSPS; and Per1, Per2, Per3 and CLOCK with diurnal preference (Katzenberg et al, 1998;Iwase et al, 2002;Archer et al, 2003;Johansson et al, 2003;Takano et al, 2004;Carpen et al, 2005;Mishima et al, 2005;Xu et al, 2005;Carpen et al, 2006;Vanselow et al, 2006). This suggests a connection between proper mood regulation and a normal functioning circadian clock.…”

Section: A Generally Disrupted Clockmentioning

confidence: 99%

Circadian genes, rhythms and the biology of mood disorders

McClung

2007

Pharmacology & Therapeutics

574

386

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For many years, researchers have suggested that abnormalities in circadian rhythms may underlie the development of mood disorders such as bipolar disorder, major depression and seasonal affective disorder. Furthermore, some of the treatments that are currently employed to treat mood disorders are thought to act by shifting or "resetting" the circadian clock, including total sleep deprivation and bright light therapy. There is also reason to suspect that many of the mood stabilizers and antidepressants used to treat these disorders may derive at least some of their therapeutic efficacy by affecting the circadian clock. Recent genetic, molecular and behavioral studies implicate individual genes that make up the clock in mood regulation. As well, important functions of these genes in brain regions and neurotransmitter systems associated with mood regulation is becoming apparent. In this review, the evidence linking circadian rhythms and mood disorders, and what is known about the underlying biology of this association, is presented.

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“…They were IVS7+79A/G (rs1522112) in intron 7, 1476G/A (rs1056478) in exon 13, and 1963A/G (rs3762836) in exon 17. Two missense mutations in exon 17 reported in a study on sleep disorder patients also did not seem to be present in our population (Iwase et al 2002). This could be the effect of population stratification whereby the SNPs were population-specific or geographically restricted.…”

Section: Discussionmentioning

confidence: 52%

“…The only coding variant identified in this study, 2102T/C, was a silent polymorphism previously identified from mutation screening in individuals suffering from sleep disorders (Iwase et al 2002). Another polymorphism reported in the literature, 3092T/C (also known as 3111T/C) was reportedly associated with the diurnal preference of evening type in Caucasians (Katzberg et al 1998), but the association was not replicated (Robilliard et al 2002).…”

Section: Discussionmentioning

confidence: 56%

“…Following the identification of the mouse gene, the human Clock gene has also been cloned (Steeves et al 1999). Although the circadian system was implicated in so many different diseases, to-date there has been only one report on the extensive screening of the hClock gene for sequence alterations (Iwase et al 2002). In this study, we present the results from denaturing high-performance liquid chromatography (dHPLC) screening of all the exons identified for the gene, including all the coding regions and the 5¢ and 3¢ untranslated regions (UTRs) and adjacent intronic regions.…”

Section: Introductionmentioning

confidence: 99%

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Identification of human Clock gene variants by denaturing high-performance liquid chromatography

Chen

Tan

2004

J Hum Genet

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The human Clock gene (hClock) encodes the CLOCK protein essential for the function of the circadian system. We have screened the entire coding region, including the 5¢ and 3¢ untranslated regions (UTRs) and the flanking intronic regions, of the hClock gene for sequence variations in 70 unrelated Chinese Singaporeans with denaturing high-performance liquid chromatography (dHPLC). A total of 15 sequence variations were detected, five of which were novel. All involved single base changes. There were 12 substitutions and three insertions/deletions. All except one were found in the introns or the UTRs. Frequencies of the minor allele for all 15 polymorphisms ranged from 0.7% to almost 50%. For the eight sites whose minor allele frequency was found to be at least 10%, pair-wise comparisons revealed that all except one were in almost complete linkage disequilibrium. Our identification of additional single nucleotide polymorphisms in the hClock gene would provide markers whose frequencies could be established in the selected population and used for further analysis of the phenotypic effects. Our results would also be useful for better planning in the selection of polymorphisms for future genetic association studies involving the hClock gene.

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Mutation screening of the human Clock gene in circadian rhythm sleep disorders

Cited by 130 publications

References 20 publications

Association between polymorphisms in the Clock gene, obesity and the metabolic syndrome in man

Association between polymorphisms in the Clock gene, obesity and the metabolic syndrome in man

Circadian genes, rhythms and the biology of mood disorders

Identification of human Clock gene variants by denaturing high-performance liquid chromatography

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