LAUSR

Purpose 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. Methods 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. Results 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. Conclusion 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.