Genetic variants of vitamin D metabolism-related DHCR7/NADSYN1 locus and CYP2R1 gene are associated with clinical features of Parkinson's disease.

PURPOSE/AIM OF THE STUDY: Parkinson's disease (PD) is the second most common neurodegenerative disorder. Vitamin D deficiency is suggested to be related to PD. A genome-wide association study indicated that genes involved in vitamin D metabolism affect vitamin D levels. Among these genes, single nucleotide polymorphisms (SNPs) of the vitamin D receptor (VDR) and vitamin D binding protein (VDBP/GC) genes have also been demonstrated to be associated with PD risk. Our aim was to investigate the relevance of SNPs within the 7-dehydrocholesterol reductase/nicotinamide adenine dinucleotide synthetase 1 (DHCR7/NADSYN1) locus and vitamin D 25-hydroxylase (CYP2R1) gene, which encode important enzymes that play a role in the vitamin D synthesis pathway, with PD and its clinical features. MATERIALS AND METHODS: Genotypes of 382 PD patients and 240 cognitively healthy individuals were evaluated by a LightSNiP assay for a total of 10 SNPs within the DHCR7/NADSYN1 locus and CYP2R1 gene. RESULTS: There were no significant differences in the allele and genotype distributions of any of the SNPs between any patient groups and healthy subjects. However, our results indicated that all of the SNPs within the DHCR7/NADSYN1 locus and CYP2R1 gene, except rs1993116, were associated with clinical motor features of PD including initial predominant symptom, freezing of gait (FoG) and falls as well as disease stage and duration of the disease. CONCLUSIONS: In conclusion, genetic variants of the DHCR7/NADSYN1 locus and the CYP2R1 gene might be related to the inefficient utilization of vitamin D independent from vitamin D levels, and it might result in differences in the clinical features of PD patients.

The Association Between Clusterin and APOE Polymorphisms and Late-Onset Alzheimer Disease in a Turkish Cohort.

Previous studies have demonstrated that clusterin (CLU), which is also known as apolipoprotein J, is involved in the pathogenesis of Alzheimer disease (AD). In this study, we investigated the association between rs2279590, rs11136000, and rs9331888 single-nucleotide polymorphisms (SNPs) in CLU and apolipoprotein E (APOE) genotypes in a cohort of Turkish patients with late-onset AD (LOAD). There were 183 patients with LOAD and 154 healthy controls included in the study. The CLU and APOE polymorphisms were genotyped using the LightSNiP assay. The "GG" genotype of rs9331888 was significantly more frequent in patients with LOAD. The "CC" genotype of the SNP was significantly more frequent in controls. The rs9331888 "GG" genotype in patients and the "CC" genotype in controls were significantly higher in non-∊4 allele carriers of APOE The haplotype analysis showed the CLU "GCG" haplotype was a risk haplotype. Our findings indicate the rs9331888 SNP of CLU is associated with LOAD independent of APOE.

Vitamin D deficiency might pose a greater risk for ApoEɛ4 non-carrier Alzheimer's disease patients.

Vitamin D is a secosteroid hormone that shares a synthetic pathway with cholesterol. ApoE, which is involved in the transport of cholesterol, is the most significant genetic risk factor for sporadic Alzheimer's disease (AD). Surprisingly, recent studies have indicated the presence of an evolutionary juncture between these two molecules. To demonstrate this possible relationship, we investigated serum levels of 25-hydroxyvitamin-D3 (25OHD) in patients with early onset-AD (EOAD; n:22), late onset-AD (LOAD; n:72), mild cognitive impairment (MCI; n:32) and in healthy subjects (n:70). We then analyzed the correlation between 25OHD and cytokines, BDNF and Hsp90 with respect to ApoE alleles, as these molecules were investigated in our previous studies. The LOAD patients had low levels of 25OHD, but these low levels originated only from ApoEɛ4 non-carrier patients. Negative correlations were observed between serum 25OHD and TNFα, IL-1ß or IL-6 levels in healthy subjects or MCI patients, but these same correlations were positive in LOAD patients. ApoE alleles indicated that these positive correlations exist only in ɛ4 carrier LOAD patients. Consequently, our results indicate that vitamin D deficiency presents a greater risk for ApoEɛ4 non-carrier AD patients than for ɛ4 carriers. Therefore, it might be beneficial to monitor the vitamin D status of ApoEɛ4 allele non-carrier AD patients.

Beta amyloid suppresses the expression of the vitamin d receptor gene and induces the expression of the vitamin d catabolic enzyme gene in hippocampal neurons.

BACKGROUND/AIMS: The beta amyloid aggregations present in Alzheimer's disease affect neurons through various toxic alterations. The aim of this study was to determine the expression of the vitamin D receptor (VDR), 25-hydroxyvitamin D3 24-hydroxylase (an accelerator of vitamin D catabolism), and the L-type voltage-sensitive calcium channel A1C (LVSCC-A1C) in hippocampal neurons in response to beta amyloid and vitamin D treatments to test the protective effects of vitamin D and the probable effects of beta amyloid on vitamin D catabolism. METHODS: The expression of the VDR, 24-hydroxylase (24OHase) and LVSCC-A1C mRNAs were studied using quantitative real-time polymerase chain reaction, and the cytotoxicity levels were determined by an ELISA in primary hippocampal neuron cultures prepared from Sprague-Dawley rat embryos. RESULTS: Our results demonstrated that beta amyloid suppressed the expression of VDR mRNA and induced the expression of 24OHase and LVSCC-A1C mRNAs. CONCLUSION: Beta amyloid may disrupt the vitamin D-VDR pathway and cause defective utilization of vitamin D by suppressing the level of the VDR and elevating the level of 24OHase.

Vitamin D inquiry in hippocampal neurons: consequences of vitamin D-VDR pathway disruption on calcium channel and the vitamin D requirement.

Vitamin D receptor (VDR) and the enzymes involved in bioactivation of vitamin D, shown to be expressed in the central nervous system, particularly in areas affected by neurodegenerative disorders, especially in hippocampus. We showed that amyloid beta (Aß) pathology includes VDR protein depletion and vitamin D-VDR pathway disruption either induced by Aß or by VDR siRNA have very similar effects on cortical neurons. The goal of this study is to show the presence of 25 hydroxy vitamin D3-24 hydroxylase (24OHase) which is essential for vitamin D catabolism in hippocampal and cortical neurons. Additional goal is to compare the expression pattern of VDR and 24OHase both in hippocampal and in cortical neurons and to investigate the effects of VDR suppression in hippocampal neurons in order to see whether similar mechanisms work in hippocampus and cerebral cortex. Primary neuronal cultures were prepared from Sprague-dawley rat embryos. qRT-PCR was performed to determine VDR, 24OHase, and LVSCC-A1C mRNA expression levels. Cytotoxicity levels were determined by ELISA. Our findings illustrate that 24OHase mRNA was present both in hippocampal and in cortical neurons. VDR and 24OHase mRNA were higher in hippocampal neurons than the cortical ones. LVSCC-A1C mRNA levels increased in hippocampal neurons when VDR is down-regulated. Our results indicate that hippocampal neurons response to VDR suppression similar as cortical neurons, regarding calcium channel regulation. Higher gene expression of 24OHase and VDR might indicate "higher requirement of vitamin D" in hippocampus and potential consequences of vitamin D deficiency in cognitive decline, neurodegeneration, and Alzheimer's disease.

Vitamin D receptor gene haplotype is associated with late-onset Alzheimer's disease.

Vitamin D(3) is a neurosteroid that mediates its effects via the vitamin D receptor (VDR). The VDR gene is located on chromosome 12q13 and consists of 9 exons. VDR contains the DNA-binding site encoded by exons 2 and 3 and the ligand-binding site encoded by exons 4 - 9. Our earlier study showed that the ApaI polymorphic site of the VDR gene is associated with late-onset Alzheimer's disease (AD). Here, we investigated the association between additional polymorphisms of the VDR gene and AD using the same samples. Two single nucleotide polymorphisms (SNPs) in intron 8 (BsmI and Tru9I polymorphisms) and one in exon 2 (FokI polymorphism) of the VDR gene were examined in up to 108 AD patients and 115 age-matched controls. Genotypes were determined with polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) methods. Haplotype analysis also included the previously studied polymorphic sites that were recognized by TaqI (in exon 9) and ApaI (in intron 8) restriction enzymes. There was no significant difference between AD patients and controls when their genotypes for BsmI, Tru9I and FokI polymorphic sites were compared. However, the frequency of "TaubF" haplotype (alleles of TaqI, ApaI, Tru9I, BsmI and FokI, respectively), which was determined by analyzing 5 polymorphisms together, was significantly higher in the AD patient group, suggesting that this haplotype is a risk factor in AD. Our results point out a possible link between AD and certain VDR polymorphisms and indicate that individuals with these polymorphisms might be vulnerable to AD.

Gene expression profiling of primary fibrochondrocyte cultures in traumatic and degenerative meniscus lesions.

PURPOSE: This study aimed to investigate how fibroblastic and chondrocytic properties of human meniscal fibrochondrocytes are affected in culture conditions according to the type of meniscal pathology and localization, and to provide basic information for tissue-engineering studies. METHODS: Primary fibrochondrocyte cultures were prepared from meniscus samples of patients who had either traumatic tear or degeneration due to osteoarthritis. Cultures were compared in terms of mRNA expression levels of COL1A1, COL2A1, COMP1, HIF1A, HIF2A, and SOX9 and secreted total collagen and sulfated sGAG levels according to the type of meniscal pathology, anatomical localization, and the number of subcultures. RESULTS: mRNA expression levels of COL1A1, COMP1, HIF1A, HIF2A, and SOX9 were found to be increased in subsequent subcultures in all specimens. COL1A1 mRNA expression levels of both lateral and medial menisci of patients with traumatic tear were significantly higher than in patients with degenerative pathology, indicating a more fibroblastic character. P1 subculture of lateral and P3 or further subculture of medial meniscus showed more fibroblastic characteristics in patients with degenerative pathology. Furthermore, in patients with degenerative pathology, the subcultures of the lateral meniscus (especially on the inner part) presented more chondrocytic characteristics than did those of medial meniscus. CONCLUSIONS: The mRNA expression levels of the cultures showed significant differences according to the anatomical localization and pathology of the meniscus, indicating distinct chondrocytic and fibroblastic features. This fundamental knowledge would help researchers to choose more efficient cell sources for cell-seeding of a meniscus scaffold, and to generate a construct resembling the original meniscus tissue.

Low Levels of LRRK2 Gene Expression are Associated with LRRK2 SNPs and Contribute to Parkinson's Disease Progression.

Parkinson's disease (PD) is a chronic neurodegenerative disease that has relatively slow progression with motor symptoms. Leucine-rich repeat kinase 2 (LRRK2) gene mutations and polymorphisms are suggested to be associated with PD. In this study, we aimed to investigate the association between single-nucleotide polymorphisms (SNPs) of the LRRK2 gene, namely, rs11176013, rs10878371, rs11835105, and PD. Genotypes of 132 PD cases and 133 healthy individuals were determined by qRT-PCR. Haplotype analysis was performed. Additionally, LRRK2 mRNA expression levels were determined in 83 PD cases and 55 healthy subjects. The relationship between LRRK2 mRNA levels, the target SNPs, and clinical data was also investigated. Our results indicated that the "GG" genotype and "G" allele of rs11176013 and the "CC" genotype and "C" allele of rs10878371 were more frequent in cases. The "GCG" haplotype was significantly more frequent in cases. LRRK2 mRNA expression levels in patients were significantly lower than those in healthy individuals. The patients with the "CC" genotype for rs10878371 and the "GG" genotype for rs11176013 had decreased LRRK2 mRNA levels. We found that the rs11176013 "GG" genotype and the rs10878371 "CC" genotype were less frequently seen in cases with akinetic rigid or combined akinetic rigid and tremor-dominant initial symptoms. Consequently, our results demonstrate that the rs11176013 and rs10878371 polymorphisms are associated with PD in a Turkish cohort, and moreover, these results suggest that these polymorphisms may affect the expression of the LRRK2 gene and disease progression and thus play a role in the pathogenesis of PD.

A Bridge Between in vitro and in vivo Studies in Neuroscience: Organotypic Brain Slice Cultures.

In vitro and in vivo models are efficiently used systems in neuroscience research to study the brain in normal or pathological conditions. There are many advantages to these systems, yet they also have significant limitations. In vitro cell cultures offer the opportunity to investigate the cell basics or primary response of a cell population against any treatment. However, these models do not always predict in vivo behavior. In vivo animal studies constitute the most realistic platform for research and therapeutic approaches, yet they are laborious, open to secondary complications and painful or stressful for the animals from an ethical point of view. Organotypic brain slice cultures provide an in vivo-like environment since they maintain three-dimensional cytoarchitecture of the brain thus enable to study many cell types in one system and allow precise control of the microenvironment. In this review, we will focus on the history and key features of organotypic brain slice cultures as well as its preparation.

Altered Transcriptional Profile of Mitochondrial DNA-Encoded OXPHOS Subunits, Mitochondria Quality Control Genes, and Intracellular ATP Levels in Blood Samples of Patients with Parkinson's Disease.

Mitochondrial dysfunctions are significant contributors to neurodegeneration. One result or a cause of mitochondrial dysfunction might be the disruption of mtDNA transcription. Limited data indicated an altered expression of mtDNA encoded transcripts in Alzheimer's disease (AD) or Parkinson's disease (PD). The number of mitochondria is high in cells with a high energy demand, such as muscle or nerve cells. AD or PD involves increased risk of cardiomyopathy, suggesting that mitochondrial dysfunction might be systemic. If it is systemic, we should observe it in different cell types. Given that, we wanted to investigate any disruption in the regulation of mtDNA encoded gene expression in addition to PINK1, PARKIN, and ATP levels in peripheral blood samples of PD cases who are affected by a neurodegenerative disorder that is very well known by its mitochondrial aspects. Our results showed for the first time that: 1) age of onset > 50 PD sporadic (PDS) cases: mtDNA transcription and quality control genes were affected; 2) age of onset <50 PDS cases: only mtDNA transcription was affected; and 3) PD cases with familial background: only quality control genes were affected. mtDNA copy number was not a confounder. Intracellular ATP levels of PD case subgroups were significantly higher than those of healthy subjects. We suggest that a systemic dysregulation of transcription of mtDNA or mitochondrial quality control genes might result in the development of a sporadic form of the disease. Additionally, ATP elevation might be an independent compensatory and response mechanism. Hyperactive cells in AD and PD require further investigation.

Interleukin-1alpha -889 C/T polymorphism in Turkish patients with late-onset Alzheimer's disease.

BACKGROUND/AIMS: The polymorphism (rs1800587) in the 5'-flanking regulatory region at -889 of the interleukin-1alpha gene has been shown to be associated with inflammatory diseases and Alzheimer's disease (AD). The aim of the current study is to determine whether there is an association between the promoter region polymorphism of the interleukin-1alpha gene and late-onset AD in a cohort of Turkish patients. METHODS: One hundred and four subjects with dementia of the Alzheimer type and 103 age-matched controls were genotyped according to the PCR with confronting two-pair primers method. RESULTS: Although the distribution of genotypes did not significantly differ (p = 0.107), the difference between allelic frequency was nearly significant according to a chi(2) test (p = 0.05) when the controls and patients were compared. CONCLUSION: Our results showed that there is no association between the -889 C/T transition on the interleukin-1alpha gene and late-onset AD in the Turkish population.

Amyloid Beta 1-42 Alters the Expression of miRNAs in Cortical Neurons.

Recently, Aß1-42 was demonstrated to have the potential to translocate into the nucleus and to be involved in the transcriptional regulation of certain neurodegeneration-related genes. This data raises the question of whether Aß-induced neurodegeneration might include the expression of miRNAs. Thus, our aim in this study was to investigate the effects of Aß1-42 on certain miRNAs which are related with vitamin D metabolism, neuronal differentiation, development, and memory. This question was investigated in primary cortical neurons that were treated with 10 µM Aß and/or 10-8 M 1,25-dihydroxyvitamin D3 at different time points by expression analysis of let-7a-5p, miR-26b-5p, miR-27b-3p, miR-31a-5p, miR-125b-5p, and miR-192-5p with qRT-PCR. Our data indicate that amyloid pathology has effects on the expression of miRNAs. Furthermore, some of these miRNAs simultaneously regulate the proteins or the enzymes involved in neuronal metabolism. The experimental setup that we used and the data we acquired supply valuable information about the miRNAs that play a part in the Aß pathology and suggested Aß as a counterpart of vitamin D at the crossroads of neuronal differentiation, development, and memory.

G82S polymorphism of receptor for advanced glycation end products gene and serum soluble RAGE levels in mild cognitive impairment and dementia of Alzheimer's type patients in Turkish population.

Alzheimer's disease (AD) is a chronic, neurodegenaration resulting in progressive cognitive decline leading to dementia. Mild cognitive impairment (MCI) is also a clinical definition of cognitive decline without functional impairment. Receptor for advanced glycation end products (RAGE) is one of the neuronal membrane receptors that binds amyloid beta peptide (Aß) triggering Aß-related pathologic signalling mechanisms. Soluble RAGE (sRAGE) is the soluble isoform of RAGE and it collects peripheral Aß by acting as a sink, prevents both RAGE-AGE interaction and transfer of Aß into brain. In this study, an association was investigated in Turkish cohorts of patients with dementia with Alzheimer's Type (DAT) and MCI patients by measuring serum sRAGE levels and by genotyping G82S polymorphism and comparing them to healthy control (HC) subjects. Although the serum sRAGE levels showed a decreasing manner among the groups, these differences were not statistically significant (p = 0.2). This is the first study for Turkish population.

Presenilin-1 gene intronic polymorphism and late-onset Alzheimer's disease.

Presenilin-1 is known to contribute to the pathogenesis of Alzheimer's disease. The association of an intronic polymorphism (rs165932) of the presenilin-1 gene with late-onset Alzheimer's disease has been documented. However, contradicting results have been shown in different populations. The aim of the current study is to determine whether there is an association between the intronic polymorphism of the presenilin-1 gene and late-onset Alzheimer's disease in a cohort of Turkish patients. One hundred and seven participants with dementia of the Alzheimer type and 106 age-matched controls were genotyped according to BamH I restriction site in intron 8 of the presenilin-1 gene. The distribution of genotypes and alleles did not significantly differ according to chi-square test (P = .52, P = .32, respectively), when the control and patients were compared. Consequently, our results showed that the 1/1 genotype does not increase the risk of developing late-onset Alzheimer's disease in the Turkish population.

Okadaic acid-induced tau hyperphosphorylation and the downregulation of Pin1 expression in primary cortical neurons.

Hyperphosphorylation of tau leading to neurofibrillary tangles (NFT) is one of the key pathological hallmarks in neurodegenerative disorders such as Alzheimer disease (AD). Peptidyl-prolyl cis-trans isomerase (Pin1) regulates the phosphorylation of Ser/Thr sites of tau protein, and promotes microtubule assembly. In this study, we aimed to determine the effect of tau hyperphosphorylation on Pin1 expression in primary cortical neurons in order to investigate the results of the pathological process on Pin1, an important enzyme involved in various cellular mechanisms. Primary cortical neurons were prepared from embryonic day 16 -Sprague Dawley rat embryos. The cultures were treated with 25 nM okadaic acid (OKA) on day 7 in order to promote tau hyperphosphorylation. The cytotoxicity was determined with LDH release and measured by ELISA. Tau phosphorylation was confirmed by western blot using anti-tau antibodies Thr231 and Tau-1. Pin1 mRNA expression level was determined by qRT-PCR at 8 and 24 h. Pin1 protein expression was analyzed with immunofluorescent labeling at 8 and 24 h. Tau phosphorylation on Thr231 was increased and non-phosphorylated Tau-1 was decreased in OKA treated group compared with the untreated control at 8 h of treatment. While Pin1 mRNA expression levels at 8 h post-OKA treatment were lower than that of control groups, there were no differences between OKA-treated group and control groups in Pin1 protein expression. Whereas no significant differences for Pin1 mRNA expression, protein expression levels were decreased OKA-treated group compared to control groups at 24 h of treatment. The LDH release of OKA-treated group was significantly increased at 24 h. Our study indicates that although OKA treatment suppressed Pin1 mRNA expression and induced tau phosphorylation at 8 h of treatment, its influence on Pin1 protein expression has 16 h phase delay. Given the important role of Pin1 in many cellular mechanisms these results might indicate that tau hyperphosphorylation involved in many neurodegenerative disorders may cause some alterations in brain microenvironment via Pin1.This is the first demonstration of the alteration of the Pin1 mRNA and protein expression in OKA induced model in primary cortical neurons.

Vitamin D Receptor Regulates Amyloid Beta 1-42 Production with Protein Disulfide Isomerase A3.

The challenge of understanding the biology of neuronal amyloid processing could provide a basis for understanding the amyloid pathology in Alzheimer's disease (AD). Based on our previous studies, we have suggested that AD might be the consequence of a hormonal imbalance in which the critical hormone is vitamin D. The present study primarily focused on the creation of a condition that prevents the genomic or nongenomic action of vitamin D by disrupting vitamin D receptors (VDR or PDIA3/1,25MARRS); the effects of these disruptions on the series of proteins involved in secretases that play a crucial role in amyloid pathology and on amyloid beta (Aß) production in primary cortical neurons were observed. VDR and PDIA3/1,25MARRS genes were silenced separately or simultaneously in E16 primary rat cortical neurons. The expression of target genes involved in APP processing, including Presenilin1, Presenilin2, Nicastrin, BACE1, ADAM10, and APP, was investigated with qRT-PCR and Western blot in this model. 1,25-Dihydroxyvitamin D3 treatments were used to verify any transcriptional regulation data gathered from siRNA treatments by determining the mRNA expression of the target genes. Immunofluorescence labeling was used for the verification of silencing experiments and intracellular Aß1-42 production. Extracellular Aß1-42 level was assessed with ELISA. mRNA and protein expression results showed that 1,25-dihydroxyvitamin D3 might affect the transcriptional regulation of the genes involved in APP processing. The intracellular and extracellular Aß1-42 measurements in our study support this suggestion. Consequently, we suggest that 1,25-dihydroxyvitamin D3 and its receptors are important parts of the amyloid processing pathway in neurons.

Both secreted and the cellular levels of BDNF attenuated due to tau hyperphosphorylation in primary cultures of cortical neurons.

Intracellular aggregation of hyperphosphorylated tau in neurofibrillary tangles (NFTs) is a major neuropathological hallmark of taupathies such as Alzheimer's disease. Okadaic acid (OKA) is a potent inhibitor of PP2A, leading to abnormal tau phosphorylation. Brain-derived neurotrophic factor (BDNF) is a neurotrophin that is selectively downregulated in AD. In this study, we investigated the effects of OKA induced tau hyperphosphorylation on secreted and cellular levels of BDNF in primary cortical neurons that were treated with 25nM OKA. Tau phosphorylation at threonine 231 (Thr231) sites was assessed by Western blot using antibodies against phospho-Thr231. Non-phosphorylated tau protein was detected with the Tau-1 antibody. Levels of BDNF secreted to the culture medium were determined by ELISA at the 8th and 24th hours of treatment. Cellular localization and protein expression of BDNF and tau were assessed by immunofluorescent labeling and fluorescent intensity measurements at 24h of treatment. Tau hyperphosphorylation was confirmed with increase in Thr231 and the decrease in Tau-1 signals after 8h of OKA treatment, compared with the control groups, secreted BDNF levels in the OKA-treated group were significantly lower after 24h of treatment but were not significantly different at 8h of treatment. BDNF immunoreactivity was seen in cytoplasm and neurites of the neurons in control group. BDNF immunoreactivity significantly decreased in the OKA treated group and this attenuation was significant especially at neurites. Our results suggest that the decrease in BDNF secretion and the BDNF expression might depend on the disruption of microtubule structure caused by tau hyperphosphorylation.

GC and VDR SNPs and Vitamin D Levels in Parkinson's Disease: The Relevance to Clinical Features.

Vitamin D deficiency is suggested to be associated with Parkinson's disease (PD). Our aim was to investigate the serum 25-hydroxyvitamin D3 (25OHD) levels of PD patients in Turkish cohort, to investigate any association of vitamin D binding protein (GC) genotypes with PD due to the significant role of GC in vitamin D transport, to determine whether vitamin D receptor (VDR) haplotype that we previously demonstrated to be a risk haplotype for AD is also a common haplotype for PD and to investigate any relevant consequence of serum 25OHD levels, GC or VDR genotypes on clinical features of PD. Three hundred eighty-two PD patients and 242 healthy subjects were included in this study. The serum 25OHD levels were investigated by CLIA, and GC and VDR SNPs were evaluated with LightSnip. Our results indicated a strong relationship between low serum 25OHD levels and PD (p < 0.001). rs7041 of GC and ApaI of VDR were associated with the PD risk (p < 0.05). Minor allele carriers for BsmI of VDR gene in both PD patients and healthy subjects had significantly higher levels of serum 25OHD (p < 0.05). The homozygous major allele carriers for rs2282679, rs3755967 and rs2298850 of GC gene in PD patients with slower progression had significantly higher levels of serum 25OHD (p  < 0.05). Minor allele carriers for FokI of VDR gene were more frequent in patients with advanced-stage PD (p < 0.05). Consequently, this is the first study demonstrating GC gene as a risk factor for PD. The relationship between PD's clinical features and low 25OHD or risk genotypes might have effects on PD independently.

Vitamin D and cognition in older adults: international consensus guidelines.

Hypovitaminosis D, a common condition in older adults, is associated with brain changes and dementia. Given the fast growing contribution of literature in this research field, clear guidance is needed for clinicians and researchers. International experts met at the invitational summit on "Vitamin D and cognition in older adults" in Boston, MA, July 2013. Based upon literature and expert opinion, the task force focused on key questions on the role of vitamin D in Alzheimer disease and related disorders. Each question was discussed and voted using a Delphi-like approach. Experts reached agreement that hypovitaminosis D increases the risk of cognitive decline and dementia in older adults, may alter the clinical presentation as a consequence of related comorbidities, but should not be used thus far as a diagnostic or prognostic biomarker of Alzheimer disease due to lack of specificity and insufficient evidence. Hypovitaminosis D should be screened in this population because of its high prevalence and supplemented, if necessary, but this advice was not specific to cognition. The task force agreed on 5 overarching principles related to vitamin D and cognition in older adults.

Polymorphisms at the ligand binding site of the vitamin D receptor gene and osteomalacia.

Vitamin D receptor (VDR) gene polymorphisms have been suggested as possible determinants of bone mineral density (BMD) and calcium metabolism. In this study, our aim was to determine whether there is an association between VDR gene polymorphism and osteomalacia or not. We determined ApaI and TaqI polymorphisms in the vitamin D receptor gene in 24 patients with osteomalacia and 25 age-matched healthy controls. Serum calcium, phosphorus, ALP, PTH, 25OHD levels were also examined. We used PCR and RFLP methods to test for an association between osteomalacia and polymorphisms within, intron 8 and exon 9 of the VDR gene. When the control and patients were compared for their ApaI and TaqI genotypes there was no relationship between VDR gene allelic polymorphisms and osteomalacia. Whereas a nearly significant difference for A allele was found in the allellic distribution of the patients (p=0.08). Also no association between biochemical data and VDR gene polymorphisms was observed.