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. These slides
can be retrieved under Electronic Supplementary Material.
