, Volume 59, Issue 1, pp 109–119 | Cite as

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

  • Anna Angelousi
  • Narjes Nasiri-Ansari
  • Eliana Spilioti
  • Emilia Mantzou
  • Vasiliki Kalotyxou
  • George Chrousos
  • Gregory Kaltsas
  • Eva Kassi
Original Article



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).


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.


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.


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.


Polyglandular syndrome Clock genes GR-a BMAL1 PER CLOCK 


Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interests.

Ethical approval

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.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Supplementary material

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Supplementary Information
12020_2017_1407_MOESM2_ESM.doc (61 kb)
Supplementary Information


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Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  • Anna Angelousi
    • 1
  • Narjes Nasiri-Ansari
    • 2
  • Eliana Spilioti
    • 2
  • Emilia Mantzou
    • 3
  • Vasiliki Kalotyxou
    • 4
  • George Chrousos
    • 5
  • Gregory Kaltsas
    • 1
  • Eva Kassi
    • 2
  1. 1.Department of Pathophysiology, Unit of Endocrinology, Laikon General HospitalNational and Kapodistrian University of AthensAthensGreece
  2. 2.Department of Biological Chemistry, School of MedicineNational and Kapodistrian University of AthensAthensGreece
  3. 3.Unit on Clinical and Translational Research in Endocrinology, First Department of Pediatrics, School of MedicineUniversity of Athens, “Aghia Sophia” Children’s HospitalAthensGreece
  4. 4.1st Department of Internal Medicine, Laikon General HospitalNational and Kapodistrian University of Athens, School of MedicineAthensGreece
  5. 5.First Department of Pediatrics, School of MedicineNational and Kapodistrian University of AthensAthensGreece

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