Vitamin D deficiency and genetic polymorphisms of Vitamin D-associated
genes in Parkinson's Disease
Abstract
Parkinson’s Disease (PD) and vitamin D share a unique link as Vitamin D
deficiency (VDD) prevails in PD. Thus, an in-depth understanding of
Vitamin D biology in PD might be crucial for therapeutic strategies
emphasizing Vitamin D. Specifically, explicating the effect of VDD and
genetic polymorphisms of vitamin D-associated genes in PD, like VDR
(Vitamin D Receptor) or GC (Vitamin D Binding Protein), may aid the
process along with polymorphisms of Vitamin D metabolizing genes (e.g.,
CYP2R1, CYP27A1) in PD. Literature review of single nucleotide
polymorphisms (SNPs) related to Vitamin D levels [GC (GC1-rs7041,
GC2-rs4588), CYP2R1, CYP24A1, CYP27B1] and Vitamin D function [VDR
(FokI - rs2228570, ApaI - rs7976091, BsmI-rs1544410, TaqI-rs731236)]
was conducted to explore their relationship with PD severity globally.
Furthermore, the DisGeNET database was utilized to explore the
gene-disease associations in PD, and STRING alongside Cytoscape was
utilized to identify critical genes associated with PD. VDR-FokI
polymorphism was reported to be significantly associated with PD in
Hungarian, Chinese, and Japanese populations, whereas VDR-ApaI
polymorphism was found to affect PD in the Iranian population. However,
VDR-TaqI and BsmI polymorphisms had no significant association with PD
severity. Conversely, GC1 polymorphisms reportedly affected Vitamin D
levels without influencing the disease severity. CYP2R1 (excluding
rs1993116) was also reportedly linked to clinical manifestations of PD.
Genetic polymorphisms might cause VDD despite enough sunlight exposure
and vitamin D-rich food intake, enhancing inflammation, and thereby
influencing PD pathophysiology. Knowledge of the polymorphisms
associated with vitamin D appears promising for developing new
therapeutic strategies against PD.