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.

中文翻译：

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维生素D受体基因多态性与椎间盘退变的关联。

目的在腰椎间盘退变（LDD）的背景下已经鉴定出许多候选基因和单核苷酸多态性（SNP）。但是，在大多数功能不足的研究中，LDD的定义不一致。此外，许多发现还没有被复制并且是矛盾的。我们的目标是通过定义明确的表型和可能的内表型表征LDD，并在大型（N = 1426）数据集上分析这些与候选维生素D受体（VDR）基因多态性之间的关联。方法对7个候选VDR SNP进行基因分型。进行了个体关联，单倍型和基因-基因相互作用分析。所有的退化性内表型均与一种或多种候选VDR基因变异显着相关。结果单倍型分析证实了3'之间的关联 末端VDR变体（BsmI，ApaI，TaqI）和Modic更改以及5'末端变体（Cdx2，A1012G）与终板缺陷的关系。我们还发现3'和5'端调控区域与端板缺陷之间存在显着的相互作用。根据我们的结果，VDR及其基因变异与特定的退化性LDD内表型高度相关。结论了解表型与基因变异之间的关系对于描述导致多因素，多基因变性过程和LDD相关疾病的途径至关重要。这些幻灯片可以在电子补充材料下找到。-末端调节区域和端板缺陷。根据我们的结果，VDR及其基因变体与特定的退化性LDD内表型高度相关。结论了解表型与基因变异之间的关系对于描述导致多因素，多基因变性过程和LDD相关疾病的途径至关重要。这些幻灯片可以在电子补充材料下找到。-末端调节区域和端板缺陷。根据我们的结果，VDR及其基因变体与特定的退化性LDD内表型高度相关。结论了解表型与基因变异之间的关系对于描述导致多因素，多基因变性过程和LDD相关疾病的途径至关重要。这些幻灯片可以在电子补充材料下找到。