Vitamin D receptor (VDR) gene polymorphisms and expression profile influence upon the immunological imbalance in Turner syndrome

  • L. O. Santos
  • R. Laranjeira
  • M. E. B. de A. Borborema
  • C. G. Sotero-Caio
  • A. de R. Duarte
  • J. Araújo
  • J. de Azevedo Silva
  • N. SantosEmail author
Original Article



Turner syndrome (TS) patients display considerable immune misregulation, and it is hypothesized that Vitamin D (VTD) activity may fluctuate according to Vitamin D receptor (VDR) polymorphisms and/or expression profile. To uncover a possible relationship between VDR genotype and clinical conditions in TS patients, we investigated two functional VDR variants (Cdx-2 and FokI) for allele and genotype frequencies, as well as expression profile in TS individuals versus healthy controls (HC).


We performed a genetic association study including 100 TS patients and 116 HC. Genotyping for VDR Cdx-2 G > A (rs11568820) and FokI C > T (rs2228570) was performed using Taqman Genotyping Assays. VDR gene expression was also evaluated in 15 TS and 15 HC, using fluorogenic probes by qPCR. Statistical analyses were performed using nonparametric Mann–Whitney test, with a 5% significance level (p < 0.05) to uncover differences between groups. In addition, we investigated whether shifted VDR mRNA levels were associated with Cdx-2 and FokI variants in TS patients.


We detected a significantly higher frequency of T allele (p = 0.006) as well as T/T genotype (p = 0.01) for FokI in TS patients when compared to HC. When assessing VDR expression, we identified a downregulation in TS woman (− 2.84 FC) versus HC (p < 0.001). Furthermore, C/T (11.24 FC; p = 0.01) and T/T (9.20 FC; p = 0.01) FokI genotypes were upregulated when compared to C/C reference genotype.


TS patients show different distribution of FokI polymorphism. Downregulation of VDR gene expression may contribute to immunological imbalance in TS.


Turner syndrome Autoimmunity VDR gene Polymorphisms Gene expression 



The authors wish to thank the patients, parents, and clinicians for availability that facilitated our data acquisition.


This research was supported by Fundação de Amparo a Ciência e Tecnologia do Estado de Pernambuco (FACEPE) and by Universidade Federal de Pernambuco (UFPE).

Compliance with ethical standards

Conflict of interest

 The authors have no conflicts of interest to declare.

Ethical approval

This work was approved by the Ethics Committee on Research in Human of the Institute of Integral Medicine Prof. Fernando Figueira (CEP-IMIP-Record: CEP/IMIP N° 802/06) and the Research Ethics Committee of Health Sciences Centre (CEP/CCS/UFPE-CAAE: 71308817.8.0000.5208).

Informed consent

Informed consent was obtained from all individuals participant included in this study.

Supplementary material

40618_2019_1135_MOESM1_ESM.docx (35 kb)
Supplementary material 1 (DOCX 34 kb)


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Copyright information

© Italian Society of Endocrinology (SIE) 2019

Authors and Affiliations

  1. 1.Department of GeneticsFederal University of PernambucoRecifeBrazil
  2. 2.Medical Genetic ServiceInstitute of Integral Medicine Professor Fernando FigueiraRecifeBrazil
  3. 3.Pediatric Endocrinology Service at Clinical HospitalFederal University of PernambucoRecifeBrazil
  4. 4.Laboratory of Immunopathology Keizo Asami, LIKAFederal University of PernambucoRecifeBrazil
  5. 5.Department of Ecology, Faculty of ScienceCharles UniversityPragueCzech Republic

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