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Aysun Türkanoğlu Özçelik, Tuğçe Öner, Birsen Can Demirdöğen, Vedat Semai Bek, Şeref Demirkaya, Orhan Adalı
Objective Vitamin D deficiency is known as an important risk factor in pathogenesis of atherosclerosis, which contributes to stroke development. Genetic variations including single nucleotide polymorphisms (SNPs) in enzymes involved in vitamin D metabolism can affect susceptibility to the development of stroke. Therefore, the objective of this study was to investigate the association between polymorphisms of vitamin D metabolizing enzymes (rs927650 SNP in CYP24A1, and rs10741657 SNP in CYP2R1 genes,) and ischemic stroke risk in Turkish population...
March 12, 2018: Neurological Research
Yi-Bang Cheng, Qian-Hui Guo, Dong-Yan Zhang, Ying Wang, Qi-Fang Huang, Chang-Sheng Sheng, Ji-Guang Wang, Jan A Staessen, Yan Li
OBJECTIVE: Carotid-femoral pulse wave velocity (cfPWV) was associated with serum parathyroid hormone (PTH) in untreated Chinese. We investigated in the same cohort whether cfPWV, brachial-ankle (baPWV) and heart-brachial (hbPWV) pulse wave velocity (PWV) were associated with rs6127099 (CYP24A1) and rs4074995 (RGS14). A previously published genome-wide association study demonstrated that each additional copy of the T (rs6127099) or G (rs4074995) allele was associated with a 7% or 3% higher serum PTH, respectively...
March 5, 2018: Blood Pressure
Iveta Bartonkova, Enikoe Kallay, Zdenek Dvorak
The role of vitamin D receptor (VDR) in immune responses has been broadly studied and it has been shown that activated VDR alters the levels of some interleukins (ILs). In this study, we studied the opposite, i.e. whether 13 selected pro-inflammatory and anti-inflammatory ILs influence the transcriptional activity of human VDR. The experimental models of choice were two human stably transfected gene reporter cell lines IZ-VDRE and IZ-CYP24, which were designed to evaluate the transcriptional activity of VDR...
2018: PloS One
Holly P Quach, Tamara Dzekic, Paola Bukuroshi, K Sandy Pang
Vitamin D3 and the synthetic vitamin D analogs, 1α-hydroxyvitamin D3 [1α(OH)D3 ] and 1α-hydroxyvitamin D2 [1α(OH)D2 ], and 25-hydroxyvitamin D3 [25(OH)D3 ] were appraised for their vitamin D receptor (VDR) associated-potencies as cholesterol lowering agents in mice in vivo. These precursors require activation in vivo: 1α(OH)D3 and 1α(OH)D2 are activated by liver Cyp2r1 and Cyp27a1 to active VDR ligands, 1α,25-dihydroxyvitamin D3 [1,25(OH)2 D3 ] and 1α,25-dihydroxyvitamin D2 [1,25(OH)2 D2 ], respectively...
February 27, 2018: Biopharmaceutics & Drug Disposition
Hemamalini Ketha, Tom D Thacher, Sara S Oberhelman, Philip R Fischer, Ravinder J Singh, Rajiv Kumar
OBJECTIVE: Supplementing lactating mothers with high doses of vitamin D3 can adequately meet vitamin D requirements of the breastfed infant. We compared the effect of bolus versus daily vitamin D3 dosing in lactating mothers on vitamin D3 catabolism. We hypothesized that catabolism of 25(OH)D3 to 24,25(OH)2 D3 would be greater in the bolus than in the daily dose group. DESIGN, SETTING AND PATIENTS: Randomized controlled trial (clinicaltrials.govNCT01240265) in 40 lactating women...
February 24, 2018: Bone
K N Liu, H X Meng, J X Hou
OBJECTIVE: There is asingle nucleotide polymorphism (SNP) in the exon 2 of the vitamin D receptor (VDR) gene that can be distinguished using the restriction endonuclease FokI, and accordingly divided into three genotypes: FF, Ff and ff. VDR-FokI polymorphism was the only known SNP that could alter the protein structure of VDR. CYP24A1 is the gene encoding vitamin D 24 hydroxylase and is a vitamin D responsive gene. The influence of rs2228570 on transcriptional activation by VDR in human gingival fibroblasts (hGF) and periodontal ligament cells (hPDLC) was investigated in this study...
February 18, 2018: Beijing da Xue Xue Bao. Yi Xue Ban, Journal of Peking University. Health Sciences
Kyosuke Satake, Toru Amano, Tadao Okamoto
Vitamin D3 (VD3 ) analogues-containing ointments are known to occasionally cause hypercalcemia in psoriasis patients, and the frequency of hypercalcemia is suggested to vary based on the VD3 analogue used. In this study, to address the differences in calcemic effects of VD3 -containing ointments, the calcemic effects of marketed VD3 -containing ointments, including calcipotriol (Cal), maxacalcitol (Max), tacalcitol (Tac), calcipotriol/betamethasone dipropionate (Cal/BDP) and maxacalcitol/betamethasone butyrate propionate (Max/BBP) ointments, were evaluated in a rat model of imiquimod-induced dermatitis...
February 21, 2018: European Journal of Pharmacology
Sisi Cao, Xiao-Li Dong, Ming-Xian Ho, Wen-Xuan Yu, Ka-Chun Wong, Xin-Sheng Yao, Man-Sau Wong
Oleanolic acid (OA) is a triterpenoid with reported bone anti-resorption activities. The present study aimed to characterize its bone protective effects in vivo and to study its effects on vitamin D metabolism, both in vivo and in vitro. OA significantly increased bone mineral density, improved micro-architectural properties, reduced urinary Ca excretion, increased 1,25(OH)₂D₃ and renal CYP27B1 mRNA expression in mature C57BL/6 ovariectomised (OVX) mice. OA also improved bone properties, Ca balance, and exerted modulatory effects on renal CYP27B1 and CYP24A1 expressions in aged normal female Sprague-Dawley rats...
February 22, 2018: Nutrients
Jeffrey D Roizen, Dong Li, Lauren O'Lear, Muhammad K Javaid, Nicholas J Shaw, Peter R Ebeling, Hanh H Nguyen, Christine P Rodda, Kenneth E Thummel, Tom D Thacher, Hakon Hakonarson, Michael A Levine
Genetic forms of vitamin D-dependent rickets (VDDRs) are due to mutations impairing activation of vitamin D or decreasing vitamin D receptor responsiveness. Here we describe two unrelated patients with early-onset rickets, reduced serum levels of the vitamin D metabolites 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D, and deficient responsiveness to parent and activated forms of vitamin D. Neither patient had a mutation in any genes known to cause VDDR, however, using whole exome sequence analysis we identified a recurrent de novo missense mutation c...
February 20, 2018: Journal of Clinical Investigation
Emma Davidson Peiris, Raghav Wusirika
CYP24A1 is an enzyme that inactivates vitamin D. Loss-of-function mutations in this enzyme are rare but have been linked with idiopathic infantile hypercalcemia as well as adult-onset nephrocalcinosis and nephrolithiasis. Genetic testing for this mutation should be considered in the presence of calciuria, elevated serum calcium, elevated 1,25-dihydroxyvitamin D, and suppressed parathyroid hormone. We present a case with these lab findings as well as an elevated 25-hydroxyvitamin D/24,25-dihydroxyvitamin D ratio in whom compound heterozygous CYP24A1 mutations were found...
September 2017: Case Reports in Nephrology and Dialysis
Jessica Cusato, Amedeo De Nicolò, Lucio Boglione, Fabio Favata, Alessandra Ariaudo, Simone Mornese Pinna, Chiara Carcieri, Federica Guido, Valeria Avataneo, Giuseppe Cariti, Giovanni Di Perri, Antonio D'Avolio
Vitamin D levels and genetic variants were associated with drug outcome/toxicity and concentrations. The plasma exposure of GS-331007, the main sofosbuvir metabolite, has been related to SVR. We evaluated the impact of polymorphisms in genes (CYP27B1, CYP24A1, VDBP and VDR) related to vitamin D pathway on sofosbuvir and GS-331007 plasma levels in HCV mono-infected patients at one month of treatment. Polymorphisms were investigated through real-time PCR; drug plasma quantification was performed through a UHPLC-MS/MS method...
February 13, 2018: Infection, Genetics and Evolution
Songcheng Yu, Xing Li, Yan Wang, Zhenxing Mao, Chongjian Wang, Yue Ba, Wenjie Li
AIMS: Association between T2DM and vitamin D was found in many epidemiologic reports. And 24-hydroxylase encoded by CYP24A1 is the very enzyme that degrades the active vitamin D metabolite. We aimed to investigate the association between rs4809957 in CYP24A1 and T2DM, as well as vitamin D level. METHODS: A total of 419 pedigrees containing 1556 participants were included. T2DM diagnosis, 25(OH)D measurement and genotyping of rs4809957 were conducted for all the individual...
January 12, 2018: Journal of Diabetes and its Complications
Kaori Yasuda, Eri Tohyama, Masashi Takano, Atsushi Kittaka, Miho Ohta, Shinichi Ikushiro, Toshiyuki Sakaki
Our previous study revealed that the 2α-substituted vitamin D analog 2α-[2-(tetrazol-2-yl)ethyl]-1α,25(OH)2D3(AH-1) exhibited a higher osteocalcin promoter transactivation activity in human osteosarcoma cells and a greater effect on bone mineral density in a rat model of osteoporosis than 1α,25(OH)2D3 without increasing blood calcium concentration. Thus, we hypothesized that AH-1 could be a promising therapeutic agent for osteoporosis without any serious side effects. In this study, we compared the CYP24A1-dependent metabolism of AH-1 with that of 1α,25(OH)2D3...
February 6, 2018: Journal of Steroid Biochemistry and Molecular Biology
Sang R Lee, Mi-Young Park, Hyun Yang, Geun-Shik Lee, Beum-Soo An, Bae-Kuen Park, Eui-Bae Jeung, Eui-Ju Hong
Androgens act in concert with vitamin D to influence reabsorption of calcium. However, it is unclear whether androgens directly regulate vitamin D homeostasis or control other cellular events that are related to vitamin D metabolism. To examine whether the expression of vitamin D-related genes in mouse kidney is driven by androgens or androgen-dependent effects, the androgen receptor and other sex steroid receptors were monitored in orchidectomized mice treated with 5α-dihydrotestosterone (DHT). Our results revealed that exposing orchidectomized mice to DHT inhibited the expression of progesterone receptor (Pgr) with or without estrogen receptor α expression, the latter was confirmed by ER-positive (MCF7 and T47D) or -negative (PCT) cells analysis...
February 2018: Journal of Molecular Endocrinology
Ryouhei Yoshikawa, Hironori Yamamoto, Otoki Nakahashi, Tomohiro Kagawa, Mari Tajiri, Mari Nakao, Shiori Fukuda, Hidekazu Arai, Masashi Masuda, Masayuki Iwano, Eiji Takeda, Yutaka Taketani
In this study, we investigated the relationship between age-related changes in renal α-Klotho gene expression, vitamin D metabolism and the responsiveness of dietary phosphate in 1, 2 and 13 month-old mice fed a high phosphate (phosphate 1.2%) diet or low phosphate (phosphate 0.02%) diet for 5 days. We found that 1,25-dihydroxyvitamin D levels in plasma were significantly lower in the high phosphate group than the low phosphate group for 1 and 2 month-old mice, but not 13 month-old mice. In addition, in the high phosphate group plasma 1,25-dihydroxyvitamin D levels were decreased in 2 month-old mice relative to 1 month-old mice, but 13 month-old mice had higher levels than 2 month-old mice...
January 2018: Journal of Clinical Biochemistry and Nutrition
D Fernando Estrada
Mitochondrial cytochromes P450 (P450s) are responsible for important metabolic reactions, including steps involved in steroid and vitamin D metabolism. The mitochondrial P450 24A1 (CYP24A1) is responsible for deactivation of the bioactive form of vitamin D, 1,25(OH)2D3. Its function relies on formation of a P450-redox partner complex with the ferredoxin and electron donor adrenodoxin (Adx). However, very little is known about how the Adx-CYP24A1 complex forms. In this study, we report the results of solution NMR in which we monitor isotopically labeled full-length Adx as it binds CYP24A1 in complex with the P450 inhibitor clotrimazole...
January 25, 2018: Journal of Biological Chemistry
Zongtao Lin, Srinivasa R Marepally, Emily S Y Goh, Chloe Y S Cheng, Zorica Janjetovic, Tae-Kang Kim, Duane D Miller, Arnold E Postlethwaite, Andrzej T Slominski, Robert C Tuckey, Carole Peluso-Iltis, Natacha Rochel, Wei Li
20S-hydroxyvitamin D3 [20S(OH)D3] is anti-inflammatory and not hypercalcemic, suggesting its potential as a lead compound. In this study, side chain modified 20S(OH)D3 analogs (4, 13, 23 and 33) together with their 1α-OH derivatives were synthesized and their metabolism and biological activities tested. 4, 13 and 23 are good substrates for CYP27B1, enabling enzymatic synthesis of their 1α-OH derivatives 5, 14 and 24. However, 33 could not be hydroxylated by CYP27B1 and acts as an inhibitor. All analogs were poorer substrates for CYP24A1 than calcitriol, indicating improved catabolic stability...
January 24, 2018: Scientific Reports
Songcheng Yu, Xing Li, Yan Wang, Zhenxing Mao, Chongjian Wang, Yue Ba, Wenjie Li
Association between T2DM and vitamin D deficiency has been reported in many epidemiologic studies. 24-hydroxylase encoded by CYP24A1 is the enzyme that degrades the active vitamin D metabolite. Variation in CYP24A1 may be associated with T2DM. This study investigates the association between rs2248359 in CYP24A1 and T2DM by a family-based association test (FBAT) and in a case-control study. The FBAT results revealed that there was transmission disequilibrium for allele T in both additive model (Z = 2.041, P = 0...
January 22, 2018: Scientific Reports
Jessica Cusato, Lucio Boglione, Amedeo De Nicolò, Fabio Favata, Alessandra Ariaudo, Simone Mornese Pinna, Federica Guido, Valeria Avataneo, Marco Cantù, Chiara Carcieri, Giuseppe Cariti, Giovanni Di Perri, Antonio D'Avolio
PURPOSE: Since HCV infection may lead to hepatocellular carcinoma (HCC) and vitamin D (deficiency) is related to cancer, we investigated if SNPs in genes involved in vitamin D pathway could predict HCV-related HCC presence in patients treated with new anti-HCV drugs. METHODS: Patients with chronic hepatitis C and treated with direct-acting antivirals were enrolled. SNPs in VDR, CYP27B1, CYP24A1 and GC genes were assessed through real-time PCR. 258 patients were analyzed...
January 22, 2018: Cancer Chemotherapy and Pharmacology
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
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