Association of vitamin D receptor gene polymorphisms with disc degeneration
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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.
KeywordsVDR 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.
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