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

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Abstract

Purpose

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).

Methods

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.

Results

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.

Conclusion

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

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Acknowledgements

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

Funding

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

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Authors and Affiliations

  1. Department of Genetics, Federal University of Pernambuco, Av. da Engenharia, s/n, Cidade Universitária, Recife, Pernambuco, 50740-600, Brazil

    L. O. Santos, R. Laranjeira, M. E. B. de A. Borborema, C. G. Sotero-Caio, J. de Azevedo Silva & N. Santos

  2. Medical Genetic Service, Institute of Integral Medicine Professor Fernando Figueira, Rua dos Coelhos, 300, Boa Vista, Recife, Pernambuco, 50070-050, Brazil

    A. de R. Duarte

  3. Pediatric Endocrinology Service at Clinical Hospital, Federal University of Pernambuco, Av. da Engenharia, s/n, Cidade Universitária, Recife, Pernambuco, 50740-600, Brazil

    J. Araújo

  4. Laboratory of Immunopathology Keizo Asami, LIKA, Federal University of Pernambuco, Av. Prof. Moraes Rego, Cidade Universitária, Recife, Pernambuco, 52171-011, Brazil

    J. de Azevedo Silva

  5. Department of Ecology, Faculty of Science, Charles University, Vinicna 7, Praha 2, 128 44, Prague, Czech Republic

    C. G. Sotero-Caio

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  1. L. O. Santos
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  2. R. Laranjeira
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  7. J. de Azevedo Silva
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  8. N. Santos
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Correspondence to N. Santos.

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 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).

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Santos, L.O., Laranjeira, R., Borborema, M.E.B.A. et al. Vitamin D receptor (VDR) gene polymorphisms and expression profile influence upon the immunological imbalance in Turner syndrome. J Endocrinol Invest 43, 505–513 (2020). https://doi.org/10.1007/s40618-019-01135-1

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