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. These slides can be retrieved under Electronic Supplementary Material.
Keywords: Endophenotype; Haplotype; Lumbar disc degeneration; Single-nucleotide polymorphism; VDR.