The etiology of Parkinson's disease (PD) is presumably multifactorial and likely involves interactions between genetic and environmental factors, as well as mitochondrial dysfunction, oxidative stress and inflammation. Among environmental factors, Vitamin D was reported to associate with the risk of PD. Vitamin D activity is mediated by its binding to the vitamin D Receptor (VDR), a transcriptional factor for almost 3% of human genes. We genotyped for ApaI, BsmI, TaqI, FokI and rs1989969 VDR single nucleotide polymorphisms (SNPs) a cohort of 406 PD and 800 healthy controls (HC) and found a strong association between the FokI (rs2228570) VDR SNP and PD. Thus, the TT genotype and the T allele resulted associated with PD in the overall analyzed PD population. Gender-based stratification of data indicated that results were maintained for FokI TT genotype and T allele in male PD patients, whereas the FokI T allele alone was confirmed as a risk factor for PD in females. Co-segregation analyses indicated the TaqI ApaI FokI rs1989969 GCTG as a “risk” haplotype for PD. In a subgroup of patients and controls neural Vitamin D and VDR concentration was analyzed in extravesicles (NDEVs) isolated from peripheral blood: no differences emerged between PD and HC. NDEVs results will need to be validated in ampler cohort but we can speculate that, if at neuronal level the amounts of Vitamin D and of VDR are comparable, than the bioavailability of vitamin D and the efficacy of the vitamin D/VDR axis is differentially modulated in PD by VDR SNPs.

帕金森病 (PD) 的病因可能是多因素的，可能涉及遗传和环境因素之间的相互作用，以及线粒体功能障碍、氧化应激和炎症。在环境因素中，据报道维生素 D 与 PD 的风险相关。维生素 D 活性是通过与维生素 D 受体 (VDR) 结合来介导的，VDR 是几乎 3% 的人类基因的转录因子。我们对Apa I、Bsm I、TaqI、Fok I 和 rs1989969 VDR单核苷酸多态性 (SNP) 的 406 名 PD 和 800 名健康对照 (HC) 进行了基因分型，发现 FokI (rs2228570) VDRSNP 和 PD。因此，TT 基因型和 T 等位基因在整个分析的 PD 群体中与 PD 相关。基于性别的数据分层表明，男性 PD 患者的Fok I TT 基因型和 T 等位基因的结果保持不变，而单独的Fok I T 等位基因被证实是女性 PD 的危险因素。共分离分析表明 TaqI ApaI FokI rs1989969 GCTG 作为 PD 的“风险”单倍型。在一组患者和对照组中，分析了从外周血中分离出的囊外 (NDEV) 中的神经维生素 D 和 VDR 浓度：PD 和 HC 之间没有出现差异。NDEVs 结果需要在更广泛的队列中进行验证，但我们可以推测，如果在神经元水平上维生素 D 和 VDR 的量相当，则维生素 D 的生物利用度和维生素 D/VDR 轴的功效受到差异调节通过VDR SNP在 PD 中。