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Altered expression of circadian clock genes in polyglandular autoimmune syndrome type III

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Abstract

Purpose

Circadian timing system is a highly conserved, ubiquitous molecular “clock” which creates internal circadian rhythmicity. Dysregulation of clock genes expression is associated with various diseases including immune dysregulation. In this study we investigated the circadian pattern of Clock-related genes in patients with polyglandular autoimmune syndrome type III (PAS type III).

Methods

Nineteen patients diagnosed with PAS type III and 12 healthy controls were enrolled. mRNA and protein expression of Clock-related genes (CLOCK, BMAL1, ROR and Per-1,-2,-3), as well as the GR-a and the GILZ genes were determined by real-time quantitative PCR and western blot analysis from blood samples drawn at 8 pm and 8am. Serum cortisol and TSH, as well as plasma ACTH, were measured by chemiluminescence.

Results

There were no statistical significant differences in the metabolic profile, cortisol, ACTH and TSH levels between patients and controls. Patients with PAS type III expressed higher transcript levels of CLOCK, BMAL1 and Per-1 in the evening than in the morning (p = 0.03, p = 0.029, p = 0.013, respectively), while the ratios (Rpm/am) of GR-a, CLOCK, BMAL1, and Per-3 mRNA levels were statistically different between patients and controls. Cortisol circadian variation (Fpm/am) was positively correlated with GILZ mRNA circadian pattern (Rpm/am) in the patient group and with the GR-a mRNA (Rpm/am) in the control group.

Conclucions

Our findings suggest that there is an aberrant circadian rhythm of Clock-related genes in patients with PAS type III. The disruption of the expression of 4 circadian Clock-related genes could indicate a possible association with the pathogenesis of the disease.

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Author notes

    Authors and Affiliations

    1. Department of Pathophysiology, Unit of Endocrinology, Laikon General Hospital, National and Kapodistrian University of Athens, Athens, 11527, Greece

      Anna Angelousi & Gregory Kaltsas

    2. Department of Biological Chemistry, School of Medicine, National and Kapodistrian University of Athens, Athens, 11527, Greece

      Narjes Nasiri-Ansari, Eliana Spilioti & Eva Kassi

    3. Unit on Clinical and Translational Research in Endocrinology, First Department of Pediatrics, School of Medicine, University of Athens, “Aghia Sophia” Children’s Hospital, Athens, 11527, Greece

      Emilia Mantzou

    4. 1st Department of Internal Medicine, Laikon General Hospital, National and Kapodistrian University of Athens, School of Medicine, Athens, 11527, Greece

      Vasiliki Kalotyxou

    5. First Department of Pediatrics, School of Medicine, National and Kapodistrian University of Athens, Athens, 11527, Greece

      George Chrousos

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    1. Anna Angelousi
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    Correspondence to Gregory Kaltsas or Eva Kassi.

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    All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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    Anna Angelousi, Narjes Nasiri-Ansari, Gregory Kaltsas and Eva Kassi authors are contributed equally to this work.

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    Angelousi, A., Nasiri-Ansari, N., Spilioti, E. et al. Altered expression of circadian clock genes in polyglandular autoimmune syndrome type III. Endocrine 59, 109–119 (2018). https://doi.org/10.1007/s12020-017-1407-1

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