Genetic Variability of the Vitamin D Receptor Affects Susceptibility to Parkinson’s Disease and Dopaminergic Treatment Adverse Events

Abstract

Vitamin D is a lipid-soluble molecule and an important transcriptional regulator in many tissues and organs, including the brain. Its role has been demonstrated also in Parkinson's disease (PD) pathogenesis. Vitamin D receptor (VDR) is responsible for the initiation of vitamin D signaling cascade. The aim of this study was to assess the associations of <i>VDR</i> genetic variability with PD risk and different PD-related phenotypes. We genotyped 231 well characterized PD patients and 161 healthy blood donors for six <i>VDR</i> single nucleotide polymorphisms, namely rs739837, rs4516035, rs11568820, rs731236, rs2228570, and rs1544410. We observed that <i>VDR</i> rs2228570 is associated with PD risk (<i>p</i> < 0.001). Additionally, we observed associations of specific <i>VDR</i> genotypes with adverse events of dopaminergic treatment. <i>VDR</i> rs1544410 (GG vs. GA + AA: <i>p</i> = 0.005; GG vs. GA: <i>p</i> = 0.009) was associated with the occurrence of visual hallucinations and <i>VDR</i> rs739837 (TT vs. GG: <i>p</i> = 0.036), rs731236 (TT vs. TC + CC: <i>p</i> = 0.011; TT vs. TC: <i>p</i> = 0.028; TT vs. CC: <i>p</i> = 0.035), and rs1544410 (GG vs. GA: <i>p</i> = 0.014) with the occurrence of orthostatic hypotension. We believe that the reported study may support personalized approach to PD treatment, especially in terms of monitoring vitamin D level and vitamin D supplementation in patients with high risk <i>VDR</i> genotypes.