• Familial vs. sporadic multiple sclerosis: VDR gene expression profile in an Iranian population
  • Sheyda Khalilian,1,* Zohreh Hojati,2 Fariba Dehghanian,3 Vahid Shaygannejad,4 Seyedeh Zahra Hosseini Imani,5 Majid Kheirollahi,6
    1. Department of Medical Genetics, School of medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran, AND Student Research Committee, School of medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran, AND USERN Office, Shahid Beheshti University of Medical Sciences, Tehra
    2. Division of Genetics, Department of Cell and Molecular Biology and Microbiology, Faculty of Biological Sciences and Technologies, University of Isfahan, Isfahan, Iran.


  • Introduction: Multiple sclerosis is an autoimmune inflammatory disease that affects the brain and spinal cord, causing the destruction of myelin and varying degrees of axonal degeneration. Many molecular mechanisms control the process of myelination in the nervous system. Alterations in each of these regulatory mechanisms lead to the impaired myelination. The Hippo signaling pathway is an important mediator of myelination in the nervous system and might contribute to the pathophysiology of MS.
  • Methods: This study examined via qPCR the RNA expression of YAP1, TAZ and CRB3 as the key effectors of the Hippo pathway and also, VDR in the peripheral blood of 72 MS patients including 35 sporadic and 37 familial MS patients; also, there were 74 healthy controls including 34 healthy first-degree relatives of the familial MS patients (HFR) and 40 healthy individuals without a family history of the disease (control).
  • Results: The results showed the increased expression of VDR in the sporadic group, as compared to other groups. There was also an increased expression of TAZ in the familial and HFR groups, as compared to the control group. The familial and sporadic patients displayed a significantly lower level of expression of YAP1 in comparison to the HFR group. The increased expression level in the sporadic patients and control group, as compared to the HFR group, was seen in CRB3, but there was no significant differential expression, as expected, in the familial group versus sporadic or HFR group. We also assessed different clinical parameters such as EDSS, onset age, family history of other autoimmune diseases and MRI characteristics of the patients. Our results showed a significant correlation between VDR expression level and EDSS in the familial patients. Moreover, the effect of brain atrophy on the relative gene expressions was evaluated in the patient groups.
  • Conclusion: Overall, these findings suggest that Hippo pathway effectors and also, VDR gene, by controlling myelination, may play a potential role in the pathophysiology of the sporadic and familial forms of MS. Confirmation of different gene expression patterns in sporadic and familial MS groups in the future may have obvious implications for the personalization of therapies in the disease.
  • Keywords: Multiple Sclerosis; Family Research; Myelin; Real-Time PCR; Medical genetics