Association of vitamin D receptor gene polymorphisms with disc degeneration

  • Adam Biczo
  • Julia Szita
  • Iain McCall
  • Peter Pal Varga
  • the Genodisc Consortium
  • Aron LazaryEmail author
Original Article



Numerous candidate genes and single-nucleotide polymorphisms (SNPs) have been identified in the background of lumbar disc degeneration (LDD). However, in most of these underpowered studies, definitions of LDD are inconsistent; moreover, many of the findings have not been replicated and are contradictory. Our aim was to characterize LDD by well-defined phenotypes and possible endophenotypes and analyse the association between these and candidate vitamin D receptor (VDR) gene polymorphisms on a large (N = 1426) dataset.


Seven candidate VDR SNPs were genotyped. Individual association, haplotype and gene–gene interaction analyses were performed. All degenerative endophenotypes were significantly associated with one or more candidate VDR gene variants.


Haplotype analyses confirmed the association between the 3′-end VDR variants (BsmI, ApaI, TaqI) and Modic changes as well as the relationship of 5′-end variants (Cdx2, A1012G) with endplate defects. We also found significant interactions between the 3′- and 5′-end regulatory regions and endplate defects. Based on our results, VDR and its gene variants are highly associated with specific degenerative LDD endophenotypes.


Understanding relationships between phenotype and gene variants is crucial for describing the pathways leading to the multifactorial, polygenic degeneration process and LDD-related conditions.

Graphic abstract

These slides can be retrieved under Electronic Supplementary Material.


VDR Lumbar disc degeneration Single-nucleotide polymorphism Haplotype Endophenotype 



The research leading to these results received funding from the European Community’s Seventh Framework Programme (FP7, 2007–2013) under Grant Agreement No. HEALTH-F2-2008-201626 (Genodisc Project). We thank Jill Urban and Jeremy Fairbank for commenting and editing the manuscript.

Compliance with ethical standards

Conflict of interest

The authors declare no conflict of interest.

Supplementary material

586_2019_6215_MOESM1_ESM.pptx (248 kb)
Supplementary material 1 (PPTX 248 kb)
586_2019_6215_MOESM2_ESM.docx (49 kb)
Supplementary material 2 (DOCX 48 kb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Adam Biczo
    • 1
    • 3
  • Julia Szita
    • 1
    • 3
  • Iain McCall
    • 2
  • Peter Pal Varga
    • 1
  • the Genodisc Consortium
  • Aron Lazary
    • 1
    Email author
  1. 1.National Center for Spinal DisordersBudapestHungary
  2. 2.Department of Diagnostic ImagingThe Robert Jones & Agnes Hunt Orthopaedic and District HospitalGobowen, OswestryUK
  3. 3.Semmelweis University School of Ph.D. StudiesBudapestHungary

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