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

Abstract

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.

The Effects of Vitamin D Deficiency on Neurodegenerative Diseases

“…In addition, recent literature underlines a potential link between prion diseases, ALS, HD, and neuropsychiatric [41,[43][44][45][46][47][48] Causal link [51][52][53][54][55][56] Vit. D levels ↓ [76][77][78][79] Severity of PD [80][81]83] Genetic link [85][86] Risk factor [96,103] Genetic predisposition [99][100][101] Causal link [109][110][111] / Non-consistent findings [132,133,136] Evidence of genetic link [137] Vit. D levels ↓ [148] Animal and cell culture studies…”

“…Consistent with several previous publications, this is also supported by two recent studies analyzing SNPs in VDR and the vitamin D-binding protein. Besides the functional VDR polymorphism, FokI was reported to be associated with cognitive decline in PD and ApaI with the risk of PD, while vitamin D-binding protein gene was suggested as a risk factor for PD [85,86]. In line with this, a double-blind, placebo-controlled intervention study from Suzuki and colleagues, including 114 PD patients, was able to reveal that supplementation of 1200 IU vitamin D 3 /day prevents disease progression in a VDR FokI genotype-dependent manner [87].…”

Genetic polymorphisms in amyotrophic lateral sclerosis: Evidence for implication in detoxification pathways of environmental toxicants

“…The Fokl functional VDR polymorphism has been associated with PD and with the cognitive decline in PD (Gatto et al, 2016;Lee et al, 2014;Niu et al, 2015). ApaI, BsmI, and TaqI polymorphisms have not been associated with susceptibility to PD (Lee et al, 2014;Niu et al, 2015).…”

Genetic, environmental and biomarker considerations delineating the regulatory effects of vitamin D on central nervous system function

“…The relationship between VDR polymorphisms, vit-D metabolite concentrations and CNS function remains unclear (136) . It has been demonstrated by multiple researchers that expression and functionality of VDR polymorphisms to transactivate specific DNA gene sequences are regulated by both genetics, environment and abundance of bioactive vit-D (128,134,137) . For example, Wilkinson et al (138) observed the TT/Tt VDR genotype of Taq1 polymorphism was associated with tuberculosis in a UK Indian population, but only in a vit-D-deficient state.…”