Abstract

Purpose/aim of the study

Parkinson’s disease (PD) is the second most common neurodegenerative disorder. Vitamin D deficiency is suggested to be related to PD. A genome-wide association study indicated that genes involved in vitamin D metabolism affect vitamin D levels. Among these genes, single nucleotide polymorphisms (SNPs) of the vitamin D receptor (VDR) and vitamin D binding protein (VDBP/GC) genes have also been demonstrated to be associated with PD risk. Our aim was to investigate the relevance of SNPs within the 7-dehydrocholesterol reductase/nicotinamide adenine dinucleotide synthetase 1 (DHCR7/NADSYN1) locus and vitamin D 25-hydroxylase (CYP2R1) gene, which encode important enzymes that play a role in the vitamin D synthesis pathway, with PD and its clinical features.

Materials and methods

Genotypes of 382 PD patients and 240 cognitively healthy individuals were evaluated by a LightSNiP assay for a total of 10 SNPs within the DHCR7/NADSYN1 locus and CYP2R1 gene.

Results

There were no significant differences in the allele and genotype distributions of any of the SNPs between any patient groups and healthy subjects. However, our results indicated that all of the SNPs within the DHCR7/NADSYN1 locus and CYP2R1 gene, except rs1993116, were associated with clinical motor features of PD including initial predominant symptom, freezing of gait (FoG) and falls as well as disease stage and duration of the disease.

Conclusions

In conclusion, genetic variants of the DHCR7/NADSYN1 locus and the CYP2R1 gene might be related to the inefficient utilization of vitamin D independent from vitamin D levels, and it might result in differences in the clinical features of PD patients.

中文翻译：

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维生素 D 代谢相关 DHCR7/NADSYN1 基因座和 CYP2R1 基因的遗传变异与帕金森病的临床特征相关

摘要

研究目的/目的

帕金森病 (PD) 是第二常见的神经退行性疾病。维生素D缺乏被认为与PD有关。一项全基因组关联研究表明，参与维生素 D 代谢的基因会影响维生素 D 水平。在这些基因中，维生素 D 受体 ( VDR ) 和维生素 D 结合蛋白 ( VDBP/GC ) 基因的单核苷酸多态性 (SNP) 也已被证明与 PD 风险相关。我们的目的是研究 7-脱氢胆固醇还原酶/烟酰胺腺嘌呤二核苷酸合成酶 1 ( DHCR7/NADSYN1 ) 基因座和维生素 D 25-羟化酶 ( CYP2R1 ) 内 SNP 的相关性) 基因，该基因编码在维生素 D 合成途径中发挥作用的重要酶，具有 PD 及其临床特征。

材料和方法

382 名 PD 患者和 240 名认知健康个体的基因型通过 LightSNiP 分析评估了DHCR7/NADSYN1基因座和CYP2R1基因内的总共 10 个 SNP。

结果

任何患者组和健康受试者之间的任何 SNP 的等位基因和基因型分布没有显着差异。然而，我们的研究结果表明，除 rs1993116 外， DHCR7/NADSYN1基因座和CYP2R1基因内的所有 SNP 都与 PD 的临床运动特征相关，包括初始主要症状、步态冻结 (FoG) 和跌倒以及疾病阶段和疾病的持续时间。

结论

总之，DHCR7/NADSYN1基因座和CYP2R1基因的遗传变异可能与维生素D的低效利用有关，而与维生素D水平无关，并可能导致PD患者临床特征的差异。