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https://www.readbyqxmd.com/read/29343764/genome-wide-association-study-in-79-366-european-ancestry-individuals-informs-the-genetic-architecture-of-25-hydroxyvitamin-d-levels
#1
Xia Jiang, Paul F O'Reilly, Hugues Aschard, Yi-Hsiang Hsu, J Brent Richards, Josée Dupuis, Erik Ingelsson, David Karasik, Stefan Pilz, Diane Berry, Bryan Kestenbaum, Jusheng Zheng, Jianan Luan, Eleni Sofianopoulou, Elizabeth A Streeten, Demetrius Albanes, Pamela L Lutsey, Lu Yao, Weihong Tang, Michael J Econs, Henri Wallaschofski, Henry Völzke, Ang Zhou, Chris Power, Mark I McCarthy, Erin D Michos, Eric Boerwinkle, Stephanie J Weinstein, Neal D Freedman, Wen-Yi Huang, Natasja M Van Schoor, Nathalie van der Velde, Lisette C P G M de Groot, Anke Enneman, L Adrienne Cupples, Sarah L Booth, Ramachandran S Vasan, Ching-Ti Liu, Yanhua Zhou, Samuli Ripatti, Claes Ohlsson, Liesbeth Vandenput, Mattias Lorentzon, Johan G Eriksson, M Kyla Shea, Denise K Houston, Stephen B Kritchevsky, Yongmei Liu, Kurt K Lohman, Luigi Ferrucci, Munro Peacock, Christian Gieger, Marian Beekman, Eline Slagboom, Joris Deelen, Diana van Heemst, Marcus E Kleber, Winfried März, Ian H de Boer, Alexis C Wood, Jerome I Rotter, Stephen S Rich, Cassianne Robinson-Cohen, Martin den Heijer, Marjo-Riitta Jarvelin, Alana Cavadino, Peter K Joshi, James F Wilson, Caroline Hayward, Lars Lind, Karl Michaëlsson, Stella Trompet, M Carola Zillikens, Andre G Uitterlinden, Fernando Rivadeneira, Linda Broer, Lina Zgaga, Harry Campbell, Evropi Theodoratou, Susan M Farrington, Maria Timofeeva, Malcolm G Dunlop, Ana M Valdes, Emmi Tikkanen, Terho Lehtimäki, Leo-Pekka Lyytikäinen, Mika Kähönen, Olli T Raitakari, Vera Mikkilä, M Arfan Ikram, Naveed Sattar, J Wouter Jukema, Nicholas J Wareham, Claudia Langenberg, Nita G Forouhi, Thomas E Gundersen, Kay-Tee Khaw, Adam S Butterworth, John Danesh, Timothy Spector, Thomas J Wang, Elina Hyppönen, Peter Kraft, Douglas P Kiel
Vitamin D is a steroid hormone precursor that is associated with a range of human traits and diseases. Previous GWAS of serum 25-hydroxyvitamin D concentrations have identified four genome-wide significant loci (GC, NADSYN1/DHCR7, CYP2R1, CYP24A1). In this study, we expand the previous SUNLIGHT Consortium GWAS discovery sample size from 16,125 to 79,366 (all European descent). This larger GWAS yields two additional loci harboring genome-wide significant variants (P = 4.7×10-9 at rs8018720 in SEC23A, and P = 1...
January 17, 2018: Nature Communications
https://www.readbyqxmd.com/read/29338102/circulating-serum-25-hydroxyvitamin-d-levels-and-bone-mineral-density-mendelian-randomization-study
#2
Susanna C Larsson, Håkan Melhus, Karl Michaëlsson
There is considerable discussion of the importance for increased serum 25-hydroxyvitamin D (S-25OHD) concentration associated with adequacy for bone health. Accordingly, whether long-term high S-25OHD concentration in general positively affects bone mineral density (BMD) is uncertain. We used a Mendelian randomization design to determine the association between genetically increased S-25OHD concentrations and BMD. Five single-nucleotide polymorphisms (SNPs) in or near genes encoding enzymes and carrier proteins involved in vitamin D synthesis or metabolism were used as instrumental variables to genetically predict one standard deviation increase in S-25OHD concentration...
January 16, 2018: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/29336863/age-associated-expression-of-vitamin-d-receptor-and-vitamin-d-metabolizing-enzymes-in-the-male-reproductive-tract-and-sperm-of-hu-sheep
#3
Xiaolei Yao, M A Ei-Samahy, Hua Yang, Xu Feng, Fengzhe Li, Fanxing Meng, Haitao Nie, Feng Wang
The cellular response to 1,25-dihydroxyvitamin D3 (Vit D3; biologically active form of Vitamin D) is complex and depends not only on Vitamin D receptor (VDR) expression but also on cellular uptake of circulating Vit D3 and the presence and activity of Vitamin D-metabolizing enzyme. This study evaluated the expression of VDR and Vitamin D-metabolizing enzymes in the ram reproductive tract at different developmental stages and in spermatozoa. Nearly all cell types in the testes and epithelial cells of the caput, corpus, and cauda expressed VDR, CYP27B1, and CYP24A1 proteins...
January 10, 2018: Animal Reproduction Science
https://www.readbyqxmd.com/read/29289621/high-dose-of-vitamin-d-supplement-is-associated-with-reduced-susceptibility-of-monocyte-derived-macrophages-to-dengue-virus-infection-and-pro-inflammatory-cytokine-production-an-exploratory-study
#4
Diana Marcela Giraldo, Andrés Cardona, Silvio Urcuqui Inchima
BACKGROUND: Dengue, one the most important public health problems in tropical and subtropical areas, is the most important mosquito-borne viral infection in humans. In the absence of effective treatment and vaccine against dengue, the active form of vitamin D could play a central role in protection against dengue virus (DENV), the causal agent of dengue. Recently we reported that monocyte-derived macrophages (MDMs) differentiated in the presence of vitamin D, in addition to expressing lower levels of mannose receptor, are less susceptible to DENV infection and produce low levels of pro-inflammatory cytokines, compared to MDMs differentiated in the absence of vitamin D...
December 28, 2017: Clinica Chimica Acta; International Journal of Clinical Chemistry
https://www.readbyqxmd.com/read/29250167/associations-between-abnormal-vitamin-d-metabolism-pathway-function-and-non-small-cell-lung-cancer
#5
Nan Ge, Xiu-Mei Chu, Yun-Peng Xuan, Dun-Qiang Ren, Yongjie Wang, Kai Ma, Hui-Jiang Gao, Wen-Jie Jiao
Lung cancer is a type of malignant tumor derived from the respiratory system, which is the leading cause of cancer-associated mortality worldwide, of which ~80% of cases are attributable to non-small cell lung cancer (NSCLC). A previous study demonstrated that 1α,25-Dihydroxyvitamin D3 (1α,25(OH)2D3), derived from the vitamin D metabolic pathway contributes an antitumor effect. Aberrant expression of the essential enzyme encoding genes, Cytochrome P450 Family 27 Subfamily A Member 1 (CYP27A1), Cytochrome P450 Family 27 Subfamily B Member 1 (CYP27B1), and Cytochrome P450 Family 24 Subfamily A Member 1 (CYP24A1) may be associated with lung cancer...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29208972/effects-of-1-25-and-24-25-vitamin-d-on-corneal-epithelial-proliferation-migration-and-vitamin-d-metabolizing-and-catabolizing-enzymes
#6
Xiaowen Lu, Zhong Chen, Namratha Mylarapu, Mitchell A Watsky
This study investigated the effects of 1,25(OH)2D3 and 24R,25(OH)2D3 on corneal epithelial cell proliferation, migration, and on the vitamin D activating enzyme CYP27B1 (produces 1,25(OH)2D3) and inactivating enzyme CYP24A1 (produces 24R,25(OH)2D3). The role of the vitamin D receptor (VDR) was also examined. In VDR wildtype mouse corneal epithelial cells (WT), 1,25(OH)2D3 increased CYP24A1 protein expression and decreased CYP27B1 expression. In VDR knockout mouse epithelial cells (KO), 1,25(OH)2D3 increased CYP24A1 and CYP27B1 protein expression...
December 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29208668/a-polymorphism-within-the-vitamin-d-transporter-gene-predicts-outcome-in-metastatic-colorectal-cancer-patients-treated-with-folfiri-bevacizumab-or-folfiri-cetuximab
#7
Martin D Berger, Sebastian Stintzing, Volker Heinemann, Shu Cao, Dongyun Yang, Yu Sunakawa, Satoshi Matsusaka, Yan Ning, Satoshi Okazaki, Yuji Miyamoto, Mitsukuni Suenaga, Marta Schirripa, Diana L Hanna, Shivani Soni, Alberto Puccini, Wu Zhang, Chiara Cremolini, Alfredo Falcone, Fotios Loupakis, Heinz-Josef Lenz
PURPOSE: Vitamin D exerts its inhibitory influence on colon cancer growth by inhibiting Wnt signaling and angiogenesis. We hypothesized that SNPs in genes involved in vitamin D transport, metabolism and signaling are associated with outcome in metastatic colorectal cancer (mCRC) patients treated with first-line FOLFIRI and bevacizumab (bev). EXPERIMENTAL DESIGN: 522 mCRC patients enrolled in the FIRE-3 (discovery cohort) and TRIBE (validation set) trials treated with FOLFIRI/bev were included in this study...
December 5, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29186865/role-of-vitamin-d-in-maintaining-renal-epithelial-barrier-function-in-uremic-conditions
#8
Milos Mihajlovic, Michele Fedecostante, Miriam J Oost, Sonja K P Steenhuis, Eef G W M Lentjes, Inge Maitimu-Smeele, Manoe J Janssen, Luuk B Hilbrands, Rosalinde Masereeuw
As current kidney replacement therapies are not efficient enough for end-stage renal disease (ESRD) treatment, a bioartificial kidney (BAK) device, based on conditionally immortalized human proximal tubule epithelial cells (ciPTEC), could represent an attractive solution. The active transport activity of such a system was recently demonstrated. In addition, endocrine functions of the cells, such as vitamin D activation, are relevant. The organic anion transporter 1 (OAT-1) overexpressing ciPTEC line presented 1α-hydroxylase (CYP27B1), 24-hydroxylase (CYP24A1) and vitamin D receptor (VDR), responsible for vitamin D activation, degradation and function, respectively...
November 26, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29186386/gene-expression-pattern-in-response-to-cholecalciferol-supplementation-highlights-cubilin-as-a-major-protein-of-25-oh-d-uptake-in-adipocytes-and-male-mice-white-adipose-tissue
#9
Lauriane Bonnet, Esma Karkeni, Charlène Couturier, Julien Astier, Julie Dalifard, Catherine Defoort, Ljubica Svilar, Jean-Charles Martin, Franck Tourniaire, Jean-François Landrier
It is well established that the active form of vitamin D, i.e. 1,25(OH)2D, regulates the expression of genes involved in its own metabolism and transport in the kidney, and possibly in the liver. However, little is known about the transcriptional impact of cholecalciferol supplementation on white adipose tissue (WAT) and adipocytes, which are a major site of vitamin D and 25(OH)D storage in the organism. To fill this gap, we investigated the impact of cholecalciferol supplementation in WAT via a panel of genes coding for enzymes and proteins involved in vitamin D metabolism and uptake...
November 24, 2017: Endocrinology
https://www.readbyqxmd.com/read/29167189/photobiodulation-inhibits-long-term-structural-and-functional-lesions-of-diabetic-retinopathy
#10
Yan Cheng, Yunpeng Du, Haitao Liu, Jie Tang, Alex Veenstra, Timothy S Kern
Previous studies demonstrated that brief (3-4 minutes), daily application of light at 670nm to diabetic rodents inhibited molecular and pathophysiologic processes implicated in the pathogenesis of diabetic retinopathy (DR), and reversed diabetic macular edema in small numbers of patients studied. Whether or not this therapy would inhibit the neural and vascular lesions that characterize the early stages of the retinopathy was unknown. We administered photobiomodulation (PBM) therapy daily for 8 months to streptozotocin-diabetic mice, and assessed effects of PBM on visual function, retinal capillary permeability, and capillary degeneration using published methods...
November 22, 2017: Diabetes
https://www.readbyqxmd.com/read/29165303/immunoreactivity-to-cyp24a1-but-not-vitamin-d-receptor-is-increased-in-mast-cells-of-keratinocyte-skin-cancers
#11
Antti Kaukinen, Hanna Siiskonen, Jukka Pelkonen, Ilkka T Harvima
In mouse skin models, mast cells have been shown to express vitamin D receptor (VDR) that can mediate the immunosuppressive effects of ultraviolet B radiation and vitamin D3. However, VDR activation leads to the expression of CYP24A1, a hydroxylase that can inactivate vitamin D3 metabolites. To examine immunoreactivity to VDR and CYP24A1 in mast cells from normal human skin, keratinocyte skin cancers, and disorders of chronic inflammation. Frozen biopsies were collected from the non-lesional and lesional skin of patients with actinic keratosis (AK), Bowen's disease/squamous cell carcinoma (SCC), basal cell carcinoma (BCC), and psoriasis...
November 22, 2017: European Journal of Dermatology: EJD
https://www.readbyqxmd.com/read/29160302/role-of-cyp24a1-vdr-and-gc-gene-polymorphisms-on-deferasirox-pharmacokinetics-and-clinical-outcomes
#12
S Allegra, J Cusato, S De Francia, A Arduino, F Longo, E Pirro, D Massano, A De Nicolò, A Piga, A D'Avolio
β-Thalassemia patients develop deficiency in vitamin D absorption and liver hydroxylation, resulting in extremely low calcitriol levels. We explored the role of single-nucleotide polymorphisms (SNPs) involved in vitamin D metabolism, transport and activity on deferasirox pharmacokinetics and outcomes (effectiveness trough levels (Ctrough) and the area under the curve (AUC) cutoffs of 20 μg ml(-1) and 360 μg ml(-1) h(-1), respectively; nonresponse AUC limit of 250 μg ml(-1) h(-1)). Ninety-nine β-thalassemic patients were enrolled...
November 21, 2017: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/29159450/lower-dietary-phosphorus-supply-in-pigs-match-both-animal-welfare-aspects-and-resource-efficiency
#13
Michael Oster, Christian Gerlinger, Kaja Heide, Franziska Just, Luisa Borgelt, Petra Wolf, Christian Polley, Brigitte Vollmar, Eduard Muráni, Siriluck Ponsuksili, Klaus Wimmers
Dietary phosphorus frequently exceeds age-specific requirements and pig manure often contains high phosphorus load which causes environmental burden at regional scales. Therefore, feeding strategies towards improved phosphorus efficiency and reduced environmental phosphorus load have to be developed. A 5-week feeding trial was conducted: piglets received medium, lower (-25%), or higher (+25%) amounts of phosphorus and calcium. Dietary responses were reflected by performance parameters, bone characteristics, and molecular data retrieved from serum, intestinal mucosa, and kidney cortex (p < 0...
November 20, 2017: Ambio
https://www.readbyqxmd.com/read/29155178/induction-of-immune-related-gene-expression-by-seminal-exosomes-in-the-porcine-endometrium
#14
Rulan Bai, Zeinab Latifi, Kazuya Kusama, Keigo Nakamura, Masayuki Shimada, Kazuhiko Imakawa
Seminal plasma (SP) is considered as a vehicle to carry sperm into female reproductive tract, of which functions have not been completely understood. This study aimed to identify the function of seminal exosomes on porcine endometrium. Exosomes were isolated from the sperm-rich fraction of boar semen and were confirmed by the expression of exosome marker HSP70 and size distribution using nano-sight tracking analysis. Porcine endometrial epithelial cells (EECs) were then treated with seminal exosomes, and RNA extracted were subjected to global expression analysis...
November 16, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29153269/vitamin-d-pathway-gene-polymorphisms-influenced-vitamin-d-level-among-pregnant-women
#15
Bule Shao, Shuying Jiang, Xiamusiye Muyiduli, Shuojia Wang, Minjia Mo, Minchao Li, Zhaopin Wang, Yunxian Yu
AIMS: To explore the relationship between vitamin D pathway genes, gene-environment interactions and vitamin D level among southeast Chinese pregnant women. METHODS: 759 participants from Zhoushan Pregnant Women Cohort (ZPWC) study, were enrolled from August 2011 to April 2014 in China. Plasma 25(OH)D levels and genetic variants in vitamin D pathway (NADSYN1/DHCR7, GC, CYP3A4, CYP2R1, CYP27A1, CYP27B1, VDR, CYP24A1, and LRP2) were measured using the blood sample collected at the first trimester...
November 7, 2017: Clinical Nutrition: Official Journal of the European Society of Parenteral and Enteral Nutrition
https://www.readbyqxmd.com/read/29127362/functional-analysis-of-vdr-gene-mutation-r343h-in-a-child-with-vitamin-d-resistant-rickets-with-alopecia
#16
Min-Hua Tseng, Shih-Ming Huang, Fu-Sung Lo, Jing-Long Huang, Chih-Jen Cheng, Hwei-Jen Lee, Shih-Hua Lin
The functional study of different mutations on vitamin D receptor (VDR) gene causing hereditary vitamin D-resistant rickets (HVDRR) remains limited. This study was to determine the VDR mutation and the mechanisms of this mutation-causing phenotype in a family with HVDRR and alopecia. Phenotype was analyzed, and in vitro functional studies were performed. The proband and his affected sister exhibited typical HVDRR with alopecia, and their biochemical and radiographic abnormalities but not alopecia responded to supraphysiological doses of active vitamin D3...
November 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29099735/effect-of-pharmacogenetic-markers-of-vitamin-d-pathway-on-deferasirox-pharmacokinetics-in-children
#17
Sarah Allegra, Jessica Cusato, Silvia De Francia, Filomena Longo, Elisa Pirro, Davide Massano, Antonio Piga, Antonio D'Avolio
OBJECTIVES: Patients with β-thalassemia major have extremely low vitamin D levels, owing to reduced intestinal absorption, subicteric tint, and/or iron-induced higher pigmentation. We investigated whether some polymorphisms within the VDR, CYP24A1, CYP27B1, and GC genes could play a role in deferasirox pharmacokinetics in a cohort of pediatric patients. PATIENTS AND METHODS: Eighteen children with β-thalassemia were enrolled. Drug plasma concentrations at the end of dosing interval (Ctrough) and after 0, 2, 4, 6, and 24 h of drug administration were measured by a HPLC-UV method...
November 2, 2017: Pharmacogenetics and Genomics
https://www.readbyqxmd.com/read/29093562/glucocorticoid-exposure-induces-preeclampsia-via-dampening-1-25-dihydroxyvitamin-d3
#18
Dongxin Zhang, Ji Zeng, Xili Miao, Haojing Liu, Liangfang Ge, Wei Huang, Jinyu Jiao, Duyun Ye
The pathogenesis of preeclampsia (PE) involves a number of biological processes that may be directly or indirectly affected by glucocorticoid (GC) and vitamin D. GC exposure increases the risk of PE, and 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) deficiency may result in PE. The purpose of the present study was to confirm the involvement of GC/1,25-(OH)2D3 axis in the pathogenesis of PE. In the study, cortisol levels of PE patients were found to be higher than that of non-complicated pregnancies, while 1,25-(OH)2D3 were decreased in both PE women and GC-induced PE rats...
November 2, 2017: Hypertension Research: Official Journal of the Japanese Society of Hypertension
https://www.readbyqxmd.com/read/29089453/calcitriol-regulates-immune-genes-cd14-and-cd180-to-modulate-lps-responses-in-human-trophoblasts
#19
Mark S Longtine, Silvija Cvitic, Bryanne N Colvin, Baosheng Chen, Gernot Desoye, D Michael Nelson
We assessed the response of primary cultures of placental villous mononucleated trophoblasts and multinucleated syncytiotrophoblast to calcitriol, the most biologically active form of vitamin D. Whole-genome microarray data showed that calcitriol modulates the expression of many genes in trophoblasts within 6 hours of exposure and RT-qPCR revealed similar responses in cytotrophoblasts, syncytiotrophoblasts and villous explants. Both cytotrophoblasts and syncytiotrophoblasts expressed genes for the vitamin D receptor, for LRP2 and CUBN that mediate internalization of calcidiol, for CYP27B1 that encodes the enzyme that converts calcidiol into active calcitriol, and for CYP24A1 that encodes the enzyme that modifies calcitriol and calcidiol to inactive calcitetrol...
December 2017: Reproduction: the Official Journal of the Society for the Study of Fertility
https://www.readbyqxmd.com/read/29080637/genetic-and-racial-differences-in-the-vitamin-d-endocrine-system
#20
REVIEW
Roger Bouillon
Twin studies indicate that genetic factors may explain about 50% of the variation of serum 25-hydroxyvitamin D (25OHD). Polymorphisms of 3 genes, delta-7-sterol-reductase, CYP2R1, and DBP/GC (and maybe CYP24A1) combined, can explain about 5% to 10% of the variation in serum 25OHD. These polymorphisms are found in nearly all populations. The variation in serum 25OHD found in different areas and populations in the world is mainly due to environmental and lifestyle factors, not truly dependent on racial differences...
December 2017: Endocrinology and Metabolism Clinics of North America
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