Genetic variants of vitamin D metabolism-related DHCR7/NADSYN1 locus and CYP2R1 gene are associated with clinical features of Parkinson’s disease

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.

Keywords:

• Parkinson’s disease
• vitamin D
• DHCR7/NADSYN1
• CYP2R1
• single nucleotide polymorphism

Disclosure statement

No potential conflict of interest was reported by the authors.

Author contributions

Merve Alaylıoğlu: Formal analysis, Investigation, Writing – original draft. Erdinç Dursun: Conceptualization, Methodology, Formal analysis, Investigation, Writing – Reviewing and Editing, Supervision. Gençer Genç: Resources. Büşra Şengül: Formal analysis, Investigation. Başar Bilgiç: Resources. Ayşegül Gündüz: Resources. Hülya Apaydın: Resources. Güneş Kızıltan: Resources. Hakan Gürvit: Resources. Haşmet Hanağası: Resources. Özgür Öztop Çakmak: Resources. Sibel Ertan: Resources. Selma Yılmazer: Supervision. Duygu Gezen-Ak: Conceptualization, Methodology, Formal analysis, Investigation, Writing – Reviewing and Editing, Funding acquisition, Supervision.

Additional information

Funding

This work was supported by the Research Fund of Istanbul University-Cerrahpasa [Project Nos.: 21712 and 27781].