Leiden University Medical Center, Department of Cardiology, C5-P, PO Box 9600, 2300 RC Leiden, The Netherlands.
Expert Opin Ther Targets. 2010 Mar;14(3):243-51. doi: 10.1517/14728220903520929.
Restenosis is the main drawback of percutaneous coronary intervention (PCI). Inherited factors may explain part of the risk of restenosis. Recently, the vitamin D receptor (VDR) has been shown to be involved not only in bone metabolism but also in modulating immune responses and cell proliferation. Since the inflammatory response is implicated in restenosis, VDR-gene variants could therefore contribute to the risk of restenosis.
METHODS/RESULTS: Systematic genotyping for 15 haplotype tagging single-nucleotide polymorphisms (SNPs) of the VDR gene was performed with the high throughput TaqMan allelic discrimination assays in the Genetic Determinants of Restenosis (GENDER) population. A haplotype-based survival analysis revealed an association of haplotypes in blocks 2, 3 and 4 of the VDR-gene with the risk of clinical restenosis (p-values 0.01, 0.04 and 0.02 respectively). After adjustment for clinical risk factors for restenosis, the individual effect of the block 2 AA haplotype (p = 0.011) persisted.
The present study indicates that VDR plays a role in restenosis after PCI. Therefore, VDR genotype may be used as risk marker for restenosis and may contribute to individual patient screening prior to PCI in clinical practice.
再狭窄是经皮冠状动脉介入治疗（PCI）的主要缺点。遗传因素可能部分解释了再狭窄的风险。最近，维生素 D 受体（VDR）不仅参与骨代谢，而且还参与调节免疫反应和细胞增殖。由于炎症反应与再狭窄有关，因此 VDR 基因变异可能导致再狭窄的风险增加。
方法/结果：在遗传决定再狭窄（GENDER）人群中，使用高通量 TaqMan 等位基因鉴别检测系统对 VDR 基因的 15 个单核苷酸多态性（SNP）进行了系统基因分型。基于单倍型的生存分析显示，VDR 基因的 2、3 和 4 块中的单倍型与临床再狭窄的风险相关（p 值分别为 0.01、0.04 和 0.02）。在调整再狭窄的临床危险因素后，2 块 AA 单倍型的个体效应仍然存在（p = 0.011）。
本研究表明，VDR 在 PCI 后再狭窄中起作用。因此，VDR 基因型可用作再狭窄的风险标志物，并可能有助于在 PCI 前对患者进行个体化筛选。
