Upregulation of vitamin D-related genes in schizophrenic patients
Received 5 June 2018
Accepted for publication 21 August 2018
Published 9 October 2018 Volume 2018:14 Pages 2583—2591
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 3
Editor who approved publication: Dr Roger Pinder
Fateme Asadzadeh Manjili,1 Seyed Mehdi Kalantar,2 Shahram Arsang-Jang,3 Soudeh Ghafouri-Fard,4 Mohammad Taheri,4,5 Arezou Sayad4
1Department of Medical Genetics, Shahid Sadoughi University of Medical Sciences, Yazd, Iran; 2Reproductive and Genetic Unit, Recurrent Abortion Research Center, Yazd Reproductive Science Institute, Yazd University of Medical Sciences, Yazd, Iran; 3Clinical Research Development Center (CRDU), Qom University of Medical Sciences, Qom, Iran; 4Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran; 5Urogenital Stem Cell Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Introduction: Low level of vitamin D is a potential risk factor for developing schizophrenia. Through interaction with its receptor (VDR) and the related enzymes (CYP27B1, CYP24A1), vitamin D modulates neurodevelopment, neuroprotection, and immunomodulation. Its deficiency leads to aberrant neurodevelopment in schizophrenic patients.
Methods: In this case–control study, relative expression of VDR, CYP27B1, and CYP24A1 in schizophrenic patients was compared with healthy individuals. Total RNA was extracted from whole blood of 50 patients with schizophrenia and 50 healthy controls. Real-time PCR was used to determine relative gene expression levels of VDR, CYP27B1, and CYP24A1.
Results: Significant upregulations were observed in VDR (P=0.004, 95% CI=0.77, 0.86), CYP27B1 (P=0.002, 95% CI=1.22, 4.98), and CYP24A1 (P≤0.0001, 95% CI=-2.721, 1.061) expressions in peripheral blood of schizophrenic patients compared with controls. Moreover, the gender-based analysis revealed upregulation of all genes in all the categories of male and female except for VDR gene in male group (P=0.234, 95% CI=-0.79, 3.35) and CYP27B1 gene in the female group (P=0.09, 95% CI=-0.21, 6.55). The age-based analysis demonstrated overexpression of VDR and CYP27B1 genes in all categories. Finally, there were significant correlations between expression levels of all genes (P<0.0001), while no correlation was found between age and expression of genes.
Conclusion: We hypothesized that the observed upregulation of the mentioned genes in schizophrenia patients might be the result of a compensatory mechanism to protect the affected individuals against adverse consequences of this disorder. Such imbalance in vitamin D processing pathway might also be implicated in the pathogenesis of schizophrenia. However, future studies should be designed to confirm the results of the current study.
Keywords: CYP27B1, CYP24A1, VDR, schizophrenia
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