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Research Article| Volume 352, ISSUE 1-2, P88-93, May 15, 2015

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

Published:April 06, 2015DOI:https://doi.org/10.1016/j.jns.2015.03.043

      Highlights

      • The study population had high lifetime ultraviolet radiation (UVR) exposure.
      • Increasing UVR exposure was not inversely associated with Parkinson's disease risk.
      • Homozygotes for rs731236 (TaqI) TT (major allele) genotype had 31% lower PD risk.
      • rs7975232 (ApaI) GG (minor allele) genotype was associated with 27% lower PD risk.
      • Vitamin D receptor gene polymorphisms may modulate risk under high UVR conditions.

      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.

      Keywords

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      References

        • McCulloch C.C.
        • et al.
        Exploring gene–environment interactions in Parkinson's disease.
        Hum Genet. 2008; 123: 257-265
        • Kiraly S.J.
        • et al.
        Vitamin D as a neuroactive substance: review.
        Sci World J. 2006; 6: 125-139
        • Eyles D.W.
        • et al.
        Distribution of the vitamin D receptor and 1 alpha-hydroxylase in human brain.
        J Chem Neuroanat. 2005; 29: 21-30
        • Sato Y.
        • Kikuyama M.
        • Oizumi K.
        High prevalence of vitamin D deficiency and reduced bone mass in Parkinson's disease.
        Neurology. 1997; 49: 1273-1278
        • van den Bos F.
        • et al.
        Bone mineral density and vitamin D status in Parkinson's disease patients.
        J Neurol. 2013; 260: 754-760
        • Suzuki M.
        • et al.
        25-Hydroxyvitamin D, vitamin D receptor gene polymorphisms, and severity of Parkinson's disease.
        Mov Disord. 2012; 27: 264-271
        • Suzuki M.
        • et al.
        Randomized, double-blind, placebo-controlled trial of vitamin D supplementation in Parkinson disease.
        Am J Clin Nutr. 2013; 97: 1004-1013
      1. Knekt, P., et al., Serum vitamin D and the risk of Parkinson disease. Arch Neurol. 67(7) 808–811.

        • Godar D.E.
        • et al.
        Solar UV doses of adult Americans and vitamin D(3) production.
        Dermatoendocrinol. 2011; 3: 243-250
        • Holick M.F.
        Vitamin D deficiency.
        N Engl J Med. 2007; 357: 266-281
      2. Kenborg, L., et al., Outdoor work and risk for Parkinson's disease: a population-based case–control study. Occup Environ Med.

        • Uitterlinden A.G.
        • et al.
        Genetics and biology of vitamin D receptor polymorphisms.
        Gene. 2004; 338: 143-156
        • Burne T.H.
        • et al.
        Behavioural characterization of vitamin D receptor knockout mice.
        Behav Brain Res. 2005; 157: 299-308
        • Han X.
        • et al.
        Vitamin D receptor gene polymorphism and its association with Parkinson's disease in Chinese Han population.
        Neurosci Lett. 2012; 525: 29-33
        • Petersen M.S.
        • et al.
        The role of vitamin D levels and vitamin D receptor polymorphism on Parkinson's disease in the Faroe Islands.
        Neurosci Lett. 2014; 561: 74-79
        • Torok R.
        • et al.
        Association of vitamin D receptor gene polymorphisms and Parkinson's disease in Hungarians.
        Neurosci Lett. 2013; 551: 70-74
        • Butler M.W.
        • et al.
        Vitamin D receptor gene as a candidate gene for Parkinson disease.
        Ann Hum Genet. 2011; 75: 201-210
        • Zhang Z.T.
        • et al.
        Association between vitamin D receptor gene polymorphisms and susceptibility to Parkinson's disease: a meta-analysis.
        Neurosci Lett. 2014; 578: 122-127
        • Li C.
        • et al.
        Vitamin D receptor gene polymorphisms and the risk of Parkinson's disease.
        Neurol Sci. 2015; 36: 247-255
        • Lee Y.H.
        • Kim J.H.
        • Song G.G.
        Vitamin D receptor polymorphisms and susceptibility to Parkinson's disease and Alzheimer's disease: a meta-analysis.
        Neurol Sci. 2014; 35: 1947-1953
        • Bodiwala D.
        • et al.
        Polymorphisms in the vitamin D receptor gene, ultraviolet radiation, and susceptibility to prostate cancer.
        Environ Mol Mutagen. 2004; 43: 121-127
        • Medeiros R.
        • et al.
        The role of vitamin D receptor gene polymorphisms in the susceptibility to prostate cancer of a southern European population.
        J Hum Genet. 2002; 47: 413-418
        • Ponsonby A.L.
        • et al.
        Variation in associations between allelic variants of the vitamin D receptor gene and onset of type 1 diabetes mellitus by ambient winter ultraviolet radiation levels: a meta-regression analysis.
        Am J Epidemiol. 2008; 168: 358-365
        • Kang G.A.
        • et al.
        Clinical characteristics in early Parkinson's disease in a central California population-based study.
        Mov Disord. 2005; 20: 1133-1142
        • Goldberg D.
        • et al.
        An effective and efficient approach for manually improving geocodes.
        Int J Health Geogr. 2008; 7: 60-79
        • Tatalovich Z.
        • et al.
        The objective assessment of lifetime cumulative ultraviolet exposure for determining melanoma risk.
        J Photochem Photobiol B. 2006; 85: 198-204
        • Hutchinson M.F.
        ANUSPLIN Version 4.3, 2003: Canberra, Australian National University, Centre for Resource and Environmental Studies.
        2003
        • McGrath J.J.
        • et al.
        A systematic review of the association between common single nucleotide polymorphisms and 25-hydroxyvitamin D concentrations.
        J Steroid Biochem Mol Biol. 2010; 121: 471-477
        • Hirschhorn J.N.
        • et al.
        A comprehensive review of genetic association studies.
        Genet Med. 2002; 4: 45-61
        • Shinpo K.
        • et al.
        Effect of 1,25-dihydroxyvitamin D(3) on cultured mesencephalic dopaminergic neurons to the combined toxicity caused by l-buthionine sulfoximine and 1-methyl-4-phenylpyridine.
        J Neurosci Res. 2000; 62: 374-382
        • Wang J.Y.
        • et al.
        Vitamin D(3) attenuates 6-hydroxydopamine-induced neurotoxicity in rats.
        Brain Res. 2001; 904: 67-75
        • Smith M.P.
        • et al.
        Calcitriol protection against dopamine loss induced by intracerebroventricular administration of 6-hydroxydopamine.
        Neurochem Res. 2006; 31: 533-539
        • Chen H.
        • Weng Q.Y.
        • Fisher D.E.
        UV signaling pathways within the skin.
        J Invest Dermatol. 2014; 134: 2080-2085
        • Maeda S.S.
        • et al.
        Seasonal variation in the serum 25-hydroxyvitamin D levels of young and elderly active and inactive adults in Sao Paulo, Brazil: the Sao PAulo Vitamin D Evaluation Study (SPADES).
        Dermatoendocrinol. 2013; 5: 211-217
        • Lawson D.E.
        • et al.
        Relative contributions of diet and sunlight to vitamin D state in the elderly.
        Br Med J. 1979; 2: 303-305
        • Macdonald H.M.
        Contributions of sunlight and diet to vitamin D status.
        Calcif Tissue Int. 2013; 92: 163-176
        • Matkovits T.
        • Christakos S.
        Ligand occupancy is not required for vitamin D receptor and retinoid receptor-mediated transcriptional activation.
        Mol Endocrinol. 1995; 9: 232-242
        • Kim J.S.
        • et al.
        Association of vitamin D receptor gene polymorphism and Parkinson's disease in Koreans.
        J Korean Med Sci. 2005; 20: 495-498
        • Lin C.H.
        • et al.
        Vitamin D receptor genetic variants and Parkinson's disease in a Taiwanese population.
        Neurobiol Aging. 2014; 35 ([1212.e11-3])
        • Lv Z.
        • et al.
        Association study between vitamin d receptor gene polymorphisms and patients with Parkinson disease in Chinese Han population.
        Int J Neurosci. 2013; 123: 60-64
        • Purdue M.P.
        • et al.
        Sun exposure, vitamin D receptor gene polymorphisms and risk of non-Hodgkin lymphoma.
        Cancer Causes Control. 2007; 18: 989-999