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

Abstract

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.

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

“…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.…”

“…VDR polymorphisms were assessed for Hardy-Weinberg Equilibrium using a chi-square test in PEG controls [30]. Haplotypes and haplotype frequencies were calculated for the FokI, TaqI, Apal and Bsml polymorphisms using PHASE 1.0 software [61].…”

“…A number of polymorphisms in the VDR gene have been identified [27]. Although findings from epidemiologic studies of PD risk investigating genetic variability in VDR have not been consistent [28, 29]and have differed across populations studied, we and others have suggested associations between VDR polymorphisms including BsmI, FokI, ApaI and TaqI and PD susceptibility [30–36], and others variants have been suggested to affect PD age of onset [37]. Although some research supports correlations between VDR polymorphisms and risk of AD and MCI, or lower cognition function [38–44], to our knowledge, no study has previously examined VDR polymorphisms and cognitive decline in Caucasian patients with PD, which is the aim of the current study.…”

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

“…1). Beydoun and others have reported that VDR (BsmI/ApaI/Taq1) and megalin gene polymorphisms to correlate with age-related cognitive decline, specifically in performance tasks assessing global mental status, verbal fluency, visual/working memory and executive function (123,(131)(132)(133)(134) . Studies investigating VDR polymorphisms and cognitive indices are heterogeneic, inconclusive and exacerbated by the confounder of uncertainy in plasma and cerebral homeostasis of vit-D (135) .…”

“…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.…”