Altered expression of circadian clock genes in polyglandular autoimmune syndrome type III
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ORIGINAL ARTICLE
Altered expression of circadian clock genes in polyglandular autoimmune syndrome type III Anna Angelousi1 Narjes Nasiri-Ansari2 Eliana Spilioti2 Emilia Mantzou3 Vasiliki Kalotyxou4 George Chrousos5 Gregory Kaltsas1 Eva Kassi2 ●
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Received: 13 June 2017 / Accepted: 22 August 2017 © Springer Science+Business Media, LLC 2017
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).
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s12020-017-1407-1) contains supplementary material, which is available to authorized users. Anna Angelousi, Narjes Nasiri-Ansari, Gregory Kaltsas and Eva Kassi authors are contributed equally to this work. * Gregory Kaltsas [email protected] * Eva Kassi [email protected] 1
Department of Pathophysiology, Unit of Endocrinology, Laikon General Hospital, National and Kapodistrian University of Athens, Athens 11527, Greece
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Department of Biological Chemistry, School of Medicine, National and Kapodistrian University of Athens, Athens 11527, Greece
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. Keywords Polyglandular syndrome Clock genes GR-a BMAL1 PER CLOCK ●
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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
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1st Department of Internal Medicine, Laikon General Hospital, Nation
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