This Article Full Text (PDF) References Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Balmforth, A. J Articles by Marx, N. Search for Related Content PubMed PubMed Citation Articles by Balmforth, A. J Articles by Marx, N. Pubmed/NCBI databases Gene GEO Profiles HomoloGene UniGene Compound via MeSH Substance via MeSH Social Bookmarking                         What's this?

Inter-subject differences in constitutive expression levels of the clock gene in man

Diabetes and Cardiovascular Research in Leeds, Faculty of Medicine & Health, University of Leeds, Leeds, UK.

Peter J Grant

Diabetes and Cardiovascular Research in Leeds, Faculty of Medicine & Health, University of Leeds, Leeds, UK.

Eleanor M Scott

Diabetes and Cardiovascular Research in Leeds, Faculty of Medicine & Health, University of Leeds, Leeds, UK.

Stephen B Wheatcroft

Diabetes and Cardiovascular Research in Leeds, Faculty of Medicine & Health, University of Leeds, Leeds, UK.

Mark T Kearney

Diabetes and Cardiovascular Research in Leeds, Faculty of Medicine & Health, University of Leeds, Leeds, UK.

Bart Staels

Faculty of Pharmacy, Department of Atherosclerosis, Institut Pasteur de Lille, UR545 INSERM, 1 rue du Professeur Calmette, BP 245 59019 Lille, Cedex, France.

Nikolaus Marx

Abteilung Innere Medizin II, Universitätsklinikum Ulm, Robert Koch Strasse 8, 89081 Ulm, Germany.

Circadian rhythms are generated, both at the level of the whole organism and at the cellular level, by biological clocks involving a set of clock genes. We previously performed a randomised, placebo-controlled, double-blind trial examining the effect of six months of pioglitazone (30 mg per day) therapy on neointima volume after coronary stenting in patients with coronary artery disease but without diabetes. In a subgroup of 15 patients from each group, a whole blood sample was taken at the beginning of the trial and at an eight-week clinical follow-up for isolation of total RNA using a PAXgene system. Using real time RT-PCR with relative quantitation, we investigated whether pioglitazone treatment altered clock gene expression in RNA extracted from peripheral white blood cells (PBCs). No significant changes in clock gene expression were noted in either placebo (99±45%) or pioglitazonetreated subjects (101±35%) after eight weeks. These data potentially extend previous findings that the clock gene is constitutively expressed over 24 hours to eight weeks.

We observed a large range of inter-subject differences in expression levels of the clock gene. The difference between the mean value for the lowest expression individual (C_T 8.8) and the highest expression individual (C_T 3.7) revealed an approximately 34-fold difference in relative clock gene expression levels. These differences may arise through differences in light exposure, polymorphic variants of the clock gene affecting gene expression and/or post-transcriptional regulation. They could influence susceptibility to disruption of normal circadian rhythms, which occur in pathophysiological conditions pertaining to diabetes and cardiovascular disease.

Key Words: circadian rhythms • pioglitazone • clock gene • gene expression • inter-subject differences • diabetes • cardiovascular disease

Diabetes and Vascular Disease Research, Vol. 4, No. 1, 39-43 (2007)
DOI: 10.3132/dvdr.2007.004


CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?