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Association between vitamin D receptor gene polymorphisms and Graves’ disease: a systematic review and meta-analysis

  • Stavroula Veneti
  • Panagiotis AnagnostisEmail author
  • Fotini Adamidou
  • Aikaterini-Maria Artzouchaltzi
  • Kostas Boboridis
  • Marina Kita



The pathogenesis of Graves’ disease (GD) and orbitopathy (GO) is not completely elucidated. On the other hand, vitamin D receptor (VDR) gene polymorphisms have been associated with vulnerability to a plethora of chronic autoimmune diseases. The primary aim of this study was to synthesize evidence on the association between VDR gene polymorphisms and GD. Secondary aim was to investigate their association with GO.


A comprehensive search was conducted in PubMed, CENTRAL and Scopus, up to December 8, 2018. Data were expressed as odds ratio (OR) with 95% confidence intervals (CI). Heterogeneity was quantified with I2 index.


Ten studies were included in the qualitative and quantitative analysis. TT subtype of TaqI polymorphism was associated with an increased risk of GD compared with Tt and tt polymorphisms (OR: 1.42; 95% CI, 1.05–1.94, p = 0.025), whereas tt was associated with a lower risk of GD, compared with TT and Tt polymorphisms (OR: 0.79; 95% CI, 0.62-0.99, p = 0.043). No association was found for ApaI, BsmI, and FokI polymorphisms. The bb subtype of BsmI polymorphism was associated with a lower risk in Asian, but with a higher GD risk in Caucasian populations, compared with BB/Bb subtypes. No eligible study was found regarding the association between VDR gene polymorphisms and the risk of GO.


The TT subtype of the TaqI polymorphism was associated with a higher susceptibility for GD compared with Tt and tt. Regarding BsmI, the bb subtype was associated with increased GD risk in Caucasians, whereas it is protective in Asians.


Vitamin D receptor VDR Gene Polymorphisms Graves’ disease 


Author contributions

S.V. searched the literature, extracted and analyzed the data and wrote the first draft of the paper with P.A., who also designed the study and resolved discrepancies regarding the quality of the studies. A.-M.A. extracted and analyzed the data. F.A., K.B., and M.K. reviewed the manuscript and provided critical scientific input.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

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Supplementary Table 1.
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Supplementary Table 2.
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Supplementary Table 3.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Endocrinology and DiabetesHippokration General Hospital of ThessalonikiThessalonikiGreece
  2. 2.1st University Department of OphthalmologyAristotle University of ThessalonikiThessalonikiGreece

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