TY - JOUR
T1 - The VDR FokI (rs2228570) polymorphism is involved in Parkinson's disease
AU - Agliardi, Cristina
AU - Guerini, Franca Rosa
AU - Zanzottera, Milena
AU - Bolognesi, Elisabetta
AU - Meloni, Mario
AU - Riboldazzi, Giulio
AU - Zangaglia, Roberta
AU - Sturchio, Andrea
AU - Casali, Carlo
AU - Di Lorenzo, Cherubino
AU - Minafra, Brigida
AU - Clerici, Mario
N1 - Funding Information:
This work was supported by Italian Ministry of health [Ricerca Corrente 2020].
Publisher Copyright:
© 2021 Elsevier B.V.
PY - 2021/9/15
Y1 - 2021/9/15
N2 - The etiology of Parkinson's disease (PD) is presumably multifactorial and likely involves interactions between genetic and environmental factors, as well as mitochondrial dysfunction, oxidative stress and inflammation. Among environmental factors, Vitamin D was reported to associate with the risk of PD. Vitamin D activity is mediated by its binding to the vitamin D Receptor (VDR), a transcriptional factor for almost 3% of human genes. We genotyped for ApaI, BsmI, TaqI, FokI and rs1989969 VDR single nucleotide polymorphisms (SNPs) a cohort of 406 PD and 800 healthy controls (HC) and found a strong association between the FokI (rs2228570) VDR SNP and PD. Thus, the TT genotype and the T allele resulted associated with PD in the overall analyzed PD population. Gender-based stratification of data indicated that results were maintained for FokI TT genotype and T allele in male PD patients, whereas the FokI T allele alone was confirmed as a risk factor for PD in females. Co-segregation analyses indicated the TaqI ApaI FokI rs1989969 GCTG as a “risk” haplotype for PD. In a subgroup of patients and controls neural Vitamin D and VDR concentration was analyzed in extravesicles (NDEVs) isolated from peripheral blood: no differences emerged between PD and HC. NDEVs results will need to be validated in ampler cohort but we can speculate that, if at neuronal level the amounts of Vitamin D and of VDR are comparable, than the bioavailability of vitamin D and the efficacy of the vitamin D/VDR axis is differentially modulated in PD by VDR SNPs.
AB - The etiology of Parkinson's disease (PD) is presumably multifactorial and likely involves interactions between genetic and environmental factors, as well as mitochondrial dysfunction, oxidative stress and inflammation. Among environmental factors, Vitamin D was reported to associate with the risk of PD. Vitamin D activity is mediated by its binding to the vitamin D Receptor (VDR), a transcriptional factor for almost 3% of human genes. We genotyped for ApaI, BsmI, TaqI, FokI and rs1989969 VDR single nucleotide polymorphisms (SNPs) a cohort of 406 PD and 800 healthy controls (HC) and found a strong association between the FokI (rs2228570) VDR SNP and PD. Thus, the TT genotype and the T allele resulted associated with PD in the overall analyzed PD population. Gender-based stratification of data indicated that results were maintained for FokI TT genotype and T allele in male PD patients, whereas the FokI T allele alone was confirmed as a risk factor for PD in females. Co-segregation analyses indicated the TaqI ApaI FokI rs1989969 GCTG as a “risk” haplotype for PD. In a subgroup of patients and controls neural Vitamin D and VDR concentration was analyzed in extravesicles (NDEVs) isolated from peripheral blood: no differences emerged between PD and HC. NDEVs results will need to be validated in ampler cohort but we can speculate that, if at neuronal level the amounts of Vitamin D and of VDR are comparable, than the bioavailability of vitamin D and the efficacy of the vitamin D/VDR axis is differentially modulated in PD by VDR SNPs.
KW - FokI
KW - NDEVs
KW - Parkinson's disease
KW - Rehabilitation
KW - VDR
KW - Vitamin D
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U2 - 10.1016/j.jns.2021.117606
DO - 10.1016/j.jns.2021.117606
M3 - Article
AN - SCOPUS:85111843381
VL - 428
JO - Journal of the Neurological Sciences
JF - Journal of the Neurological Sciences
SN - 0022-510X
M1 - 117606
ER -