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 emphasising 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 metabolising genes (e.g., CYP2R1 and CYP27A1) in PD. Literature review of single nucleotide polymorphisms (SNPs) related to vitamin D levels [GC (GC1-rs7041 and GC2-rs4588), CYP2R1, CYP24A1 and CYP27B1] and vitamin D function [VDR (FokI - rs2228570 and rs10735810; ApaI - rs7976091, rs7975232BsmI and rs1544410; and TaqI - rs731236)] was conducted to explore their relationship with PD severity globally. 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, there by influencing PD pathophysiology. Knowledge of the polymorphisms associated with VDD appears promising for developing precision vitamin D-dosing therapeutic strategies against PD.