The role of vitamin D levels and vitamin D receptor polymorphism on Parkinson's disease in the Faroe Islands

Petersen, Maria Skaalum; Bech, Sára; Christiansen, Debes H.; Schmedes, Anna Vibeke; Halling, Jónrit

doi:10.1016/j.neulet.2013.12.053

Cited by 54 publications

(42 citation statements)

References 27 publications

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“…Candidate SNPs in VDR were selected based on 1) findings from previous studies assessing vitamin D genes in PD [30, 31, 34, 35, 37, 46–48], 2) previous genetic studies of vitamin D metabolism-related disorders [49, 50], 3) potential biological functional relevance of a SNP [51], and/or 4) variants in the coding region of the gene leading to an amino acid change in the protein [52]. We used Build 129 of the NCBI dbSNP, the NIEHS-sponsored GeneSNPs web portal (University of Utah Genome Center, 2007) and the NCBI OMIM database to identify candidate SNPs for genotyping.…”

Section: Methodsmentioning

confidence: 99%

Vitamin D receptor gene polymorphisms and cognitive decline in Parkinson's disease

Gatto

Paul²,

Sinsheimer

et al. 2016

Journal of the Neurological Sciences

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We and others have suggested that vitamin D receptor gene (VDR) polymorphisms influence susceptibility for Parkinson’s disease (PD), Alzheimer’s disease (AD), mild cognitive impairment (MCI) or overall cognitive functioning. Here we examine VDR polymorphisms and cognitive decline in patients with PD. Non-Hispanic Caucasian PD patients (n=190) in the Parkinson Environment Gene (PEG) study were successfully genotyped for seven VDR polymorphisms. Cognitive function was assessed with the Mini-Mental State Exam (MMSE) at baseline and at a maximum of three follow-up exams. Using repeated-measures regression we assessed associations between VDR SNP genotypes and change in MMSE longitudinally. PD cases were on average 67.4 years old at diagnosis and were followed for an average of 7.1 years into disease. Each additional copy of the FokI A allele was associated with a 0.115 decrease in the total MMSE score per year of follow-up (β = −0.115, SE(β) = 0.05, p=0.03) after adjusting for age, sex, education and PD duration. The effect on MMSE by the FokI A allele was comparable in absolute magnitude to the effect for disease duration in years prior to first interview (β = −0.129 per year, SE(β) = 0.08, p=0.13), and years of education (β = 0.118 per year, SE(β) = 0.03, p<0.001). When LD/LED use and PD subtype were added to the model, the effect of the FokI A allele on total MMSE score was magnified (β = −0.141, SE(β) = 0.05, p=0.005). Results point to Fokl, a functional VDR polymorphism, as being associated with cognitive decline in PD. Future studies examining the contributions of the vitamin D metabolic pathway to cognitive dysfunction in PD are needed.

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Section: Methodsmentioning

confidence: 99%

Vitamin D receptor gene polymorphisms and cognitive decline in Parkinson's disease

Gatto

Paul²,

Sinsheimer

et al. 2016

Journal of the Neurological Sciences

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“…Differences in findings for VDR SNPs between studies could be due to background levels of UVR exposure in the population studied. While there was not complete overlap in the polymorphisms examined, generally existing studies that included populations with very low UVR exposure [15, 16, 38], did not detect PD associations in the VDR SNPs in which we did identify associations. This could be further investigated by studying the impact of VDR genetic variation on PD in other very high or very low UVR exposed populations.…”

Section: Discussionmentioning

confidence: 75%

“…In Hungarian and Chinese case-control studies, CC+TC genotypes of FokI (SNP rs10735810 tagged the FokI restriction site) were more common than the TT genotype in PD patients[14, 16]. Other case-control studies of these RLFPs and other VDR polymorphisms including both smaller and larger numbers of cases did not find associations[15, 39, 40]. A recent two-stage GWAS study of an initial 770 non-Hispanic Caucasian PD families analyzed tag SNPs covering all common variants in and around VDR including four RFLPs we and others have examined.…”

Section: Discussionmentioning

confidence: 99%

Vitamin D receptor gene polymorphisms and Parkinson's disease in a population with high ultraviolet radiation exposure

Gatto

Sinsheimer

Cockburn

et al. 2015

Journal of the Neurological Sciences

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Introduction A high prevalence of vitamin D deficiency has been reported in Parkinson’s disease (PD). Epidemiologic studies examining variability in genes involved in vitamin D metabolism have not taken into account level of exposure to ultraviolet radiation (UVR). We examined whether exposure to UVR (as a surrogate for vitamin D levels) and variations in the vitamin D receptor gene (VDR) are associated with PD. Methods Within a geographical information system (GIS) we linked participants’ geocoded residential address data to ground level UV data to estimate historical exposure to UVR. Six SNPs in VDR were genotyped in non-Hispanic Caucasian subjects. Results Average lifetime UVR exposure levels were >5000 Wh/m2, which was higher than levels for populations in previous studies, and UVR exposure did not differ between cases and controls. Homozygotes for the rs731236 TT (major allele) genotype had a 31% lower risk of PD risk (OR = 0.69; 95% CI = 0.49, 0.98; p=0.04 for TT vs. TC + CC). The rs7975232 GG (minor allele) genotype was also associated with decreased risk of PD (OR = 0.63; 95% CI = 0.42, 0.93; p=0.02 for GG vs. TG + TT). The association between PD risk and a third locus, rs1544410 (BsmI), was not statistically significant after adjustment for covariates, although there was a trend for lower risk with the GG genotype. Conclusions This study provides initial evidence that VDR polymorphisms may modulate risk of PD in a population highly exposed to UVR throughout lifetime.

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“…Additionally, a published vitamin D intervention study has demonstrated positive effects of vitamin D supplementation on clinical rating scales in PD patients (Suzuki et al, 2013), providing clinical evidence for a potential therapeutic role for vitamin D or calcitriol. However, not all studies have found an association between vitamin D levels and PD (Petersen et al, 2014; Shrestha et al, 2016). Thus, the link between low levels of vitamin D and PD is controversial, and may only apply to some individuals with PD.…”

Section: Discussionmentioning

confidence: 96%

Reduced ability of calcitriol to promote augmented dopamine release in the lesioned striatum of aged rats

Cass

Peters

2017

Neurochemistry International

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Parkinson’s disease (PD) is a progressive and debilitating neurodegenerative disorder that affects over one million people in the United States. Previous studies, carried out in young adult rats, have shown that calcitriol, the active metabolite of vitamin D, can be neuroprotective in 6-hydroxydopamine (6-OHDA) models of PD. However, as PD usually affects older individuals, the ability of calcitriol to promote dopaminergic recovery was examined in lesioned young adult (4 month old), middle-aged (14 month old) and aged (22 month old) rats. Animals were given a single injection of 12 μg 6-OHDA into the right striatum. Four weeks later they were administered vehicle or calcitriol (1.0 μg/kg, s.c.) once a day for eight consecutive days. In vivo microdialysis experiments were carried out three weeks after the calcitriol or vehicle treatments to measure potassium and amphetamine evoked overflow of DA from both the left and right striata. In control animals treated with 6-OHDA and vehicle there were significant reductions in evoked overflow of DA on the lesioned side of the brain compared to the contralateral side. The calcitriol treatments significantly increased evoked overflow of DA from the lesioned striatum in both the young adult and middle-aged rats. However, the calcitriol treatments did not significantly augment DA overflow in the aged rats. Postmortem tissue levels of striatal DA were also increased in the young and middle-aged animals, but not in the aged animals. In the substantia nigra, the calcitriol treatments led to increased levels of DA in all three age groups. Thus, the effects of calcitriol were similar in the young adult and middle-aged animals, but in the aged animals the effects of calcitriol were diminished. These results suggest that calcitriol may help promote recovery of dopaminergic functioning in injured nigrostriatal neurons; however, the effectiveness of calcitriol may be reduced in aging.

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The role of vitamin D levels and vitamin D receptor polymorphism on Parkinson's disease in the Faroe Islands

Cited by 54 publications

References 27 publications

Vitamin D receptor gene polymorphisms and cognitive decline in Parkinson's disease

Vitamin D receptor gene polymorphisms and cognitive decline in Parkinson's disease

Vitamin D receptor gene polymorphisms and Parkinson's disease in a population with high ultraviolet radiation exposure

Reduced ability of calcitriol to promote augmented dopamine release in the lesioned striatum of aged rats

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