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 VDR genetic variability with PD risk and different PD-related phenotypes. We genotyped 231 well characterized PD patients and 161 healthy blood donors for six VDR single nucleotide polymorphisms, namely rs739837, rs4516035, rs11568820, rs731236, rs2228570, and rs1544410. We observed that VDR rs2228570 is associated with PD risk (p < 0.001). Additionally, we observed associations of specific VDR genotypes with adverse events of dopaminergic treatment. VDR rs1544410 (GG vs. GA + AA: p = 0.005; GG vs. GA: p = 0.009) was associated with the occurrence of visual hallucinations and VDR rs739837 (TT vs. GG: p = 0.036), rs731236 (TT vs. TC + CC: p = 0.011; TT vs. TC: p = 0.028; TT vs. CC: p = 0.035), and rs1544410 (GG vs. GA: p = 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 VDR genotypes.

25-Hydroxyvitamin D Serum Levels Linked to Single Nucleotide Polymorphisms (SNPs) (rs2228570, rs2282679, rs10741657) in Skeletal Muscle Aging in Institutionalized Elderly Men Not Supplemented with Vitamin D

“…The gene encoding VDR on chromosome 12q13.11 spans approximately 75 kb and contains 14 exons [ 20 ]. Among numerous (>60) SNPs identified in the VDR gene were linked to the risk of several disease such as autoimmune disorders, including rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel disease, diabetes mellitus, multiple sclerosis, an autoimmune disease, cancer or Parkinson [ 21 , 22 , 35 , 36 ]. However, these studies did not analyze the relationship between VDR polymorphisms and 25-OH D blood serum concentrations.…”

“…Biallelic variants of these SNPs generate different gene products/protein isoforms that influence the functional effect on proteins: CYP2R1 (rs10741657) differ in the working enzymatic activity of 25-hydroxylase; GC (rs2282679) differ in their vitamin D binding/transport affinity; VDR (rs2228570) differ in the functional uptake of vitamin D receptor. SNPs had a function already described in the literature based on their previous association with 25-OH/D and its related genotypes [ 13 , 18 , 21 , 22 , 23 ]. Thus, depending on the nature of the polymorphism, it could either increase or decrease the concentration of 25-OH/D in sera.…”

Associations of vitamin D receptor polymorphisms with risk of Alzheimer’s disease, Parkinson’s disease, and mild cognitive impairment: a systematic review and meta-analysis

“…After carefully reviewing the full texts, we performed a secondary screening and eliminated 257 articles due to other disease (n = 231), insufficient information (n = 3), other genes and VDR gene polymorphisms (n = 23). A total of 30 studies covering 81 studies were retained for this meta-analysis (Luedecking-Zimmer et al, 2003;Kim et al, 2005;Gezen-Ak et al, 2007Lehmann et al, 2011;Han et al, 2012;Khorram Khorshid et al, 2013;Liu et al, 2013;Lv et al, 2013;Török et al, 2013;Petersen et al, 2014;Gatto et al, 2015;Łaczmański et al, 2015;Zhou et al, 2015;Kang et al, 2016;Mohammadzadeh and Pazhouhesh, 2016;Mun et al, 2016;Meamar et al, 2017;Tanaka et al, 2017;Oliveira et al, 2018;Hu et al, 2020;Agliardi et al, 2021;Arévalo et al, 2021;Agúndez et al, 2022;Dimitrakis et al, 2022a,b;Kamyshna et al, 2022;Redenšek et al, 2022;Zhang et al, 2022).…”

25-Hydroxyvitamin D Serum Levels Linked to Single-Nucleotide Polymorphisms (SNPs) (rs2228570, rs2282679, rs10741657) in Sports Performance in CrossFit® Elite Athletes

“…VDBP is a protein belonging to the albumin family and is the main carrier of vitamin D in blood [16,17]. Finally, SNPs in the vitamin D-receptor (VDR) gene influence vitamin D biological activity in many tissues, with muscle being of particular interest in sport performance (25(OH)D) [16][17][18][19][20].…”