Glenville Jones

Queen's University, Kingston, Ontario, Canada

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Publications (93)562.1 Total impact

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    ABSTRACT: Objective: Metabolites of vitamin D in maternal-neonatal dyads remains relatively unexplored. The goal of this study was to evaluate concentrations of 25(OH)D3, 24,25(OH)2D3, and 3-epi- 25(OH)D3 in maternal-infant pairs at delivery. Methods: Serum samples of maternal and infant cord blood were collected on 131 mother-infant pairs at delivery. Vitamin D metabolites were analyzed in triplicate using LC-MS/MS. Statistical analysis was conducted using the Fisher's exact test, Wilcoxon Rank Sum test and Spearman correlation coefficients. Results: Mean 25(OH)D3 concentrations in maternal and cord blood were 32.9 and 18.5 ng/mL, respectively; mean maternal and cord 24,25(OH)2D3 were 2.0 vs. 1.1 ng/mL, respectively. Absolute concentrations of 3-epi-25(OH)D3 were similar in maternal and cord samples (2.4 vs 2.2 ng/mL), while the proportion of the total 25(OH)D as the 3-epimer was 6.5% in maternal samples and 10.5% in cord samples. This suggests that the fetus contributes significantly to 3-epi-25(OH)D3 production. In contrast, the ratio of 25(OH)D3:24,25(OH)2D3 was identical in maternal and cord samples (18.5) suggesting equivalent CYP24A1 activity in mother and fetus. Maternal and cord metabolite levels were highly correlated (r=0.78, 0.90, 0.89 for 25(OH)D3, 24,25(OH)2D3, and 3-epi-25(OH)D3 respectively, p=0.001 for all). Serum concentrations of all metabolites were lower in non-white infants compared to white infants. Maternal and cord concentrations of 25(OH)D3 were positively associated with birth weight (r=0.21, p=0.02; r = 0.25, p = 0.003, respectively). Conclusion: This data would suggest that while maternal and cord concentrations of vitamin D metabolites are highly correlated, regulation of specific vitamin D metabolites in the mother and the neonate may be mediated independently.
    No preview · Article · Oct 2015 · Journal of pediatric gastroenterology and nutrition
  • Martin Kaufmann · Seong Min Lee · J Wesley Pike · Glenville Jones
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    ABSTRACT: Vitamin D receptor (VDR)-mediated 1,25-dihydroxyvitamin D3 (1,25(OH)2D3)-dependent gene expression is compromised in the VDR null mouse. The biological consequences include: hypocalcemia, hypophosphatemia, elevated PTH and 1,25(OH)2D3, and consequential skeletal abnormalities. CYP24A1 is a cytochrome P450 enzyme that is involved in the side chain oxidation and destruction of both 1,25(OH)2D3 and 25-OH-D3. In the current studies, we used LC-MS/MS technology to compare the metabolic profiles of VDR null mice fed either a normal or a calcium and phosphate enriched rescue diet and to assess the consequence of transgenic expression of either mouse or human VDR genes in the same background. Serum 1,25(OH)2D3 levels in VDR null mice on normal chow were highly elevated (>3000 pg/mL) coincident with undetectable levels of catabolites such as 24,25-(OH)2D3 and 25-OH-D3-26,23-lactone normally observed in wildtype mice. The rescue diet corrected serum Ca(++), PTH and 1,25(OH)2D3 values and restored basal expression of Cyp24a1 as evidenced by both renal expression of Cyp24a1 and detection of 24,25-(OH)2D3 and the 25-OH-D3-26,23-lactone. Unexpectedly, this diet also resulted in supra-normal levels of 3-epi-24,25-(OH)2D3 and 3-epi-25-OH-D3-26,23-lactone. The reappearance of serum 24,25-(OH)2D3 and renal Cyp24a1 expression following rescue suggests that basal levels of Cyp24a1 may be repressed by high PTH. Introduction of transgenes for either mouse or human VDR also normalized vitamin D metabolism in VDR null mice whereas this metabolic pattern was unaffected by a transgene encoding a ligand binding-deficient mutant (L233S) human VDR. We conclude that LC-MS/MS-based metabolic profiling is an ideal analytical method to study mouse models with alterations in calcium/phosphate homeostasis.
    No preview · Article · Oct 2015 · Endocrinology
  • Glenville Jones · Martin Kaufmann
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    ABSTRACT: Liquid chromatography tandem mass spectrometry (LC-MS/MS) has emerged as the latest technology to be used to assay the metabolites of vitamin D. The method uses molecular mass as a detection technique after straightforward extraction and chromatography steps. LC-MS/MS assay provides a level of accuracy and reproducibility not seen before with other methods and is beginning to rival antibody-based methods in terms of sensitivity and convenience. Methods for detection of underivatized and DMEQ-TAD derivatized vitamin D metabolites are evaluated. Sensitivity is improved by 10-100 fold with derivatization and allows for the simultaneous assay of multiple vitamin D metabolites, a process termed vitamin D metabolite profiling. Clinical and research applications of vitamin D metabolite profiling are discussed.
    No preview · Article · Sep 2015 · The Journal of steroid biochemistry and molecular biology
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    ABSTRACT: A challenge facing serum 1,25-dihydroxyvitamin D [1,25-(OH)2D3] quantification is low circulating levels (15-60 pg/mL), requiring a selective extraction technique coupled with derivatization prior to LC-MS/MS. We compared liquid-liquid (LLE)- and immuno-extraction (IE) methods with derivatization using PTAD or DMEQ-TAD, and analyzed samples on ACQUITY/TQ-S instruments. We observed that all methods provided quantification of 20-30 pg/mL 1,25-(OH)2D3, however IE/DMEQ-TAD offered the greatest sensitivity and selectivity with an estimated LLOQ of 10 pg/mL. LLE offered the advantage of simultaneously detecting other metabolites including 25-OH-D3 and 24,25-(OH)2D3. We conclude that the choice of technique used to measure 1,25-(OH)2D3 depends on level of sensitivity required, and interest in measuring other metabolites.
    Full-text · Conference Paper · Sep 2015
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    ABSTRACT: In addition to benefits for bone health, vitamin D is implicated in muscle function in children and adults. To determine if vitamin D dosage positively correlated with gross motor development at 3 and 6 months of age. We hypothesized that higher doses would be associated with higher scores for gross motor skills. A consecutive sample of 55 healthy, term, and breastfed infants from Montreal, Canada were recruited from a randomized trial of vitamin D supplementation between 2009 and 2012. Infants were randomized to 400 International Units (IU) (n = 19), 800 IU (n = 18) or 1,200 IU (n = 18) vitamin D3/day. Motor performance at 3 and 6 months was quantified by the Alberta Infant Motor Scale (AIMS). Plasma vitamin D3 metabolites were measured by tandem mass spectrometry. AIMS scores did not differ at 3 months. However, total AIMS scores and sitting subscores were significantly higher at 6 months in infants receiving 400 IU/day compared to 800 IU/day and 1,200 IU/day groups (p < .05). There were weak negative correlations with length and C-3 epimer of 25(OH)D. In contrast to our hypothesis, gross motor achievements were significantly higher in infants receiving 400 IU/day vitamin D. Our findings also support longer infants being slightly delayed.
    Full-text · Article · Sep 2015 · Physical & Occupational Therapy in Pediatrics

  • No preview · Article · Sep 2015 · Pediatric Nephrology
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    ABSTRACT: Vitamin D status during infancy has been associated with important pediatric health outcomes; however concentrations of many vitamin D metabolites in premature infants are not yet described. The objective of this study was to evaluate concentrations of 25(OH)D3, 24,25(OH)2D3, and 3-epi-25(OH)D3 in premature infants. 32 infants <32 weeks gestation were randomized to receive 400 or 800IU/day of vitamin D3 orally. Vitamin D metabolites from serum obtained monthly were analyzed in triplicate using a novel, very sensitive Liquid Chromatography-Tandem Mass Spectrometry-based method. Statistical analysis was conducted using the Fisher's exact test, Wilcoxon Rank Sum test, and Spearman correlation coefficients. Measurements over time were fit with linear mixed effect models. A p-value of <0.05 was considered statistically significant. Mean serum 25(OH)D3 concentrations in cord blood were 17.3 ng/mL; mean 3-epi-25(OH)D3 were 1.3 ng/mL, mean 24,25(OH)2D3 were 1.4 ng/mL. Both 25(OH)D3 and 3-epi-25(OH)D3 increased significantly over time, and the percent of total 25(OH)D3 concentration that was 3-epi-25(OH)D3 also increased significantly (7.2% vs. 29.7%, p < 0.0001 for cord blood vs. 8 weeks). Serum 25(OH)D3:24,25(OH)2D3 ratios at weeks 4 and 8 were higher than ratios reported in older children and adults. Vitamin D metabolism in infants appears to have distinct differences from adults. Vitamin D supplementation was effective in raising 25(OH)D3 concentrations; however significant increases in 3-epi-25(OH)D3 also occurred. Increased 25(OH)D3: 24,25(OH)2D3 ratios in premature infants may be due to immature expression of CYP24A1. Further work is necessary to determine if there are developmental advantages to this unique vitamin D metabolism. Copyright © 2015 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.
    No preview · Article · Aug 2015 · Clinical nutrition (Edinburgh, Scotland)
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    ABSTRACT: Calcium metabolism changes in pregnancy and lactation to meet fetal needs, with increases in 1,25-dihydroxyvitamin D (1,25-(OH)2D) during pregnancy playing an important role. However, these changes rarely cause maternal hypercalcemia. When maternal hypercalcemia occurs, further investigation is essential, and disorders of 1,25-(OH)2D catabolism should be carefully considered in the differential diagnosis. A patient with a childhood history of recurrent renal stone disease and hypercalciuria presented with recurrent hypercalcemia and elevated 1,25-(OH)2D levels during pregnancy. Laboratory tests in the fourth pregnancy showed suppressed parathyroid hormone, elevated 1,25-(OH)2D, and high-normal 25-hydroxyvitamin D (25-OH-D) levels, suggesting disordered vitamin D metabolism. Analysis revealed low 24,25-dihydroxyvitamin D3 (24,25-(OH)2D) and high 25-OH-D3 levels, suggesting loss-of-function of CYP24A1 (25-OH-D3-24-hydroxylase). Gene sequencing confirmed that she was a compound heterozygote with the E143del and R396W mutations in CYP24A1. This case broadens presentations of CYP24A1 mutations and of hypercalcemia in pregnancy. Furthermore, it illustrates that patients with CYP24A1 mutations can maintain normal calcium levels during steady state but can develop hypercalcemia when challenged, such as in pregnancy when 1,25-(OH)2D levels are physiologically elevated.
    Full-text · Article · Jun 2015 · The Journal of Clinical Endocrinology and Metabolism
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    ABSTRACT: Idiopathic infantile hypercalcemia (IIH) is characterized by severe hypercalcemia with failure to thrive, vomiting, dehydration, and nephrocalcinosis. Recently, mutations in the vitamin D catabolizing enzyme 25-hydroxyvitamin D3-24-hydroxylase (CYP24A1) were described that lead to increased sensitivity to vitamin D due to accumulation of the active metabolite 1,25-(OH)2D3. In a subgroup of patients who presented in early infancy with renal phosphate wasting and symptomatic hypercalcemia, mutations in CYP24A1 were excluded. Four patients from families with parental consanguinity were subjected to homozygosity mapping that identified a second IIH gene locus on chromosome 5q35 with a maximum logarithm of odds (LOD) score of 6.79. The sequence analysis of the most promising candidate gene, SLC34A1 encoding renal sodium-phosphate cotransporter 2A (NaPi-IIa), revealed autosomal-recessive mutations in the four index cases and in 12 patients with sporadic IIH. Functional studies of mutant NaPi-IIa in Xenopus oocytes and opossum kidney (OK) cells demonstrated disturbed trafficking to the plasma membrane and loss of phosphate transport activity. Analysis of calcium and phosphate metabolism in Slc34a1-knockout mice highlighted the effect of phosphate depletion and fibroblast growth factor-23 suppression on the development of the IIH phenotype. The human and mice data together demonstrate that primary renal phosphate wasting caused by defective NaPi-IIa function induces inappropriate production of 1,25-(OH)2D3 with subsequent symptomatic hypercalcemia. Clinical and laboratory findings persist despite cessation of vitamin D prophylaxis but rapidly respond to phosphate supplementation. Therefore, early differentiation between SLC34A1 (NaPi-IIa) and CYP24A1 (24-hydroxylase) defects appears critical for targeted therapy in patients with IIH. Copyright © 2015 by the American Society of Nephrology.
    No preview · Article · Jun 2015 · Journal of the American Society of Nephrology
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    Martin Kaufmann · Glenville Jones · Billy Joe Molloy

    Full-text · Technical Report · Mar 2015
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    ABSTRACT: 24,25-Dihydroxyvitamin D [24,25(OH)2D] in serum may be both a nuisance and nutritionally valuable. We investigated the impact of 24,25(OH)2D3 on the performance of commercially available immunoassays for serum total 25-hydroxyvitamin D [25(OH)D] using (a) serum from a nationally representative sample of adults, (b) serum from a spiking experiment, and (c) data from the UK Vitamin D External Quality Assurance Scheme (DEQAS). We also investigated the utility of the serum ratio of 24,25(OH)2D3 to 25(OH)D as an index of inactivation and of response to vitamin D supplementation using randomized controlled trial (RCT) data. Measurement of 24,25(OH)2D in sera by a LC-MS/MS method allowed for an investigation of its impact on immunoassay-derived serum 25(OH)D values as well as its clinical utility. We report data from a nationally representative sample of adults, a recent vitamin D RCT in older adults, and DEQAS. 24,25(OH)2D3 contributed to the positive bias observed in some immunoassays relative to LC-MS/MS-derived estimates for total 25(OH)D. A spiking experiment showed that the degree of cross-reactivity with 24, 25(OH)2D was high and may underpin this positive bias. Adjustment for 24,25(OH)2D3 concentration brought estimates closer to true values. Data from the vitamin D RCT showed that the ratio of 24,25(OH)2D3 to 25(OH)D was associated with serum 25(OH)D3 and with response of serum 25(OH)D to vitamin D supplementation. Our findings highlight that the effect of 24,25(OH)2D3 in serum is a double-edged sword-an interferent for some immunoassays, yet potentially informative of nutritional status. © 2015 American Association for Clinical Chemistry.
    No preview · Article · Feb 2015 · Clinical Chemistry
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    ABSTRACT: Introduction The physiological role of CYP24A1 is to catabolize the active form of vitamin D, 1α,25-(OH)2D3, to its excretory form calcitroic acid, and to catabolize the circulating form 25-OH-D3 to 24,25-(OH)2D3. Inactivation of CYP24A1 leads to hypercalcemia due to excess 1α,25-(OH)2D3 action and is a cause of idiopathic infantile hypercalcemia (IIH) in man. Methods A novel LC/MS/MS assay was used to compare vitamin D serum metabolomes from IIH subjects & CYP24A1 knockout mice. 25-OH-D3 and its catabolites formed by CYP24A1 (24,25-(OH)2D3 and 25-OH-D3-26,23-lactone) were separated from their C-3-epimer isomers and quantified in a 5-minute analysis with LLOQs and CVs of 0.1-0.3 ng/mL and 4-7%, respectively. Because 24,25-(OH)2D3 levels depend on 25-OH-D3, which varies significantly with vitamin D nutrition, we expressed 24,25-(OH)2D3 as a 25-OH-D3:24,25-(OH)2D3 ratio. Results In normal vitamin D sufficient subjects (25-OH-D >20 ng/mL), the 25-OH-D3:24,25-(OH)2D3 ratio rarely rose above 25. IIH subjects exhibited reduced 24,25-(OH)2D3 levels giving elevated ratios of 75-110. Wild-type mice typically had more 24,25-(OH)2D3 but less 25-OH-D3 than humans, as indicated by a ratio of approximately 2. Levels of 24,25-(OH)2D3 were reduced in CYP24A1 knockout mice, giving ratios of 76-102, resembling the IIH subjects. Conversely, 25-OH-D3 levels rose from 15 to 103 ng/mL indicating severely impaired catabolism of the major circulating form of vitamin D. Unlike human subjects, 25-OH-D3-26,23-lactone was easily detectable in wild-type mouse serum, but almost totally absent with CYP24A1 ablation. Conclusion The low level of 24,25-(OH)2D3 observed in CYP24A1 knockout mice confirms that the analogous finding in IIH subjects is due to inactivation of CYP24A1 and emphasizes the specificity of the LC/MS/MS assay. We conclude that 25-OH-D3:24,25-(OH)2D3 ratios >80 are indicative of CYP24A1 inactivation in vivo, and that measurement of the ratio could be an important screening tool for selected clinical research samples.
    Full-text · Conference Paper · Oct 2014
  • Glenville Jones
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    ABSTRACT: Vitamin D deficiency and insufficiency are common in patients with CKD. Association studies suggest that low 25-hydroxyvitamin D3 (25-OH-D3) is a harbinger of poor outcomes in these patients. Serum 25-OH-D represents the best biomarker of vitamin D status, but there is much debate surrounding the performance of some of the assay methods. Programs such as the Vitamin D Standardization Program and Vitamin D External Quality Assessment Scheme (DEQAS) in the United Kingdom have allowed us to assess the accuracy and reproducibility of the available methods. Liquid chromatography-tandem mass spectrometry-based methods for serum 25-OH-D measurement are emerging as more accurate and reliable alternatives to the immunoassay-based methods that have dominated over the past 2 decades. There is a renewed optimism that serum 25-OH-D is a useful biomarker to be used in patients with CKD, in particular to diagnose vitamin D deficiency and monitor vitamin D therapy. This commentary discusses some of the methodologic problems associated with serum 25-OH-D assays and their resolution, and looks forward to the future of vitamin D testing.
    No preview · Article · Aug 2014 · Clinical Journal of the American Society of Nephrology

  • No preview · Conference Paper · May 2014
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    ABSTRACT: Context: The discovery of hypercalcemic diseases due to loss-of-function mutations in CYP24A1 has placed a new demand for sensitive and precise assays for 24,25-dihydroxyvitamin D. Objective: We describe a novel LC-MS/MS-based method involving derivatization with DMEQ-TAD to simultaneously assay multiple vitamin D metabolites including 25-OH-D and 24,25-(OH)2Dusing 100 μ l of serum with a 5-minute run-time. Design: The assay uses a newly-synthesized internal standard d6-24,25-(OH)2D3 enabling quantitation of 24,25-(OH)2D3, as well as the determination of the ratio of 25-OH-D3:24,25-(OH)2D3, a physiologically useful parameter. Setting: We report data on >1000 normal and disease samples involving D deficiency or hypercalcemia, as well as studies involving knockout mouse models. Results: The assay showed good correlation with samples from quality assurance schemes for 25-OH-D (25-OH-D2 and 25-OH-D3) determination (-2 to -5% bias), exhibited low inter- and intra-assay coefficients of variation (4-7%), and lower limits of quantitation of 0.25-0.45 nmol/L. In clinical studies, we found a strong correlation between serum levels of 25-OH-D3 and 24,25-(OH)2D3 (r(2)=0.80) in subjects over a broad range of 25-OH-D3 values and a marked lack of production of 24,25-(OH)2D3 below 25 nmol/L of 25-OH-D. The ratio of 25-OH-D3:24,25-(OH)2D3 which remained <25 in vitamin D sufficient subjects (serum 25-OH-D < 50 nmol/L) but was greatly elevated (80-100) in patients with idiopathic infantile hypercalcemia (IIH). Conclusions: The new method also showed good utility in clinical settings involving vitamin D deficiency, supplementation with vitamin D and IIH, as well as in animal models with ablation of selected CYPs involved in vitamin D.
    Full-text · Article · Mar 2014 · The Journal of Clinical Endocrinology and Metabolism
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    ABSTRACT: Although no gold standard exists, liquid chromatography tandem mass spectrometry (LC-MS/MS) is a precise and accurate method for the analysis of plasma 25-hydroxyvitamin D (25(OH)D). Immunoassays are more readily available and require small volume sampling, ideal for infant testing. The objective was to compare two commercially available immunoassays for measuring circulating 25(OH)D concentration in infant plasma against LC-MS/MS. Capillary blood samples from 103 infants were analyzed for plasma 25(OH)D using an enzyme immunoassay (EIA, Octeia, IDS Ltd.) and radioimmunoassay (RIA, DiaSorin). Plasma 25(OH)D3, the C-3 epimer of 25(OH)D3 (3-epi-25(OH)D3) and 24,25-dihydroxyvitamin D (24,25(OH)2D3) were measured on the same samples using LC-MS/MS. To establish whether plasma 24,25(OH)2D3 or 3-epi-25(OH)D3 interfere with these immunoassay results, the zero 25(OH)D calibrator from each assay kit was spiked with increasing amounts of 24,25(OH)2D3 or 3-epi-25(OH)D3. Classifying infants below the common vitamin D status targets of 50nmol/L and 75nmol/L respectively, 58% and 99% fell below using the RIA, 19% and 56% with the EIA and 31% and 76% with LC-MS/MS. Compared to LC-MS/MS, both immunoassays showed poor Bland-Altman limits of agreement for 25(OH)D concentrations (RIA: limits of agreement -27 to +13%; EIA: -12 to +41%), and mountain plots (folded cumulative distribution) depicted significant skew and bias. Spiked 24,25(OH)2D3 concentrations, but not 3-epi-25(OH)D3, appeared as >100% of known values on the EIA but not on the RIA thus, suggesting that the EIA may cross react with 24,25(OH)2D3 to a greater extent than 3-epi-25(OH)D3. Two common immunoassays resulted in very different classifications of vitamin D status possibly related to the interference of other vitamin D metabolites. Based on these data, LC-MS/MS assessment of vitamin D status is recommended in young infants (4-6weeks of age).
    No preview · Article · Jan 2014 · Bone
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    ABSTRACT: Context: Hypercalcemia, hypercalciuria, and recurrent nephrolithiasis are all common clinical problems. This case report illustrates a newly-described but possibly not uncommon cause of this presenting complex. Objective: Report a patient studied for over 30 years ,with the diagnosis finally made with modern biochemical and genetic tools. Design: Case report and review of literature Setting: University Referral Center Patient: Single patient with hypercalcemia, hypercalciuria, and recurrent nephrolithiasis Intervention: Treatment with low calcium diet, low vitamin D intake, prednisone, and ketoconazole. Main Outcome Measure: Clinical and biochemical response to interventions above. Results: Calcium absorption by dual isotope absorptiometry was elevated at 37.4%. Serum levels of 24,25-dihydroxyvitamin D were very low as measured in two laboratories (0.62ng/mL, nl 3.49+/-1.57, and 0.18mg/mL). Genetic analysis of CYP24A1 revealed homozygous mutation E143del previously described. The patient's serum calcium and renal function improved markedly on treatment with ketoconazole but not with prednisone. Conclusions: Chronic hypercalcemia, hypercalciuria, and/or nephrolithiasis may be caused by mutations in CYP24A1 causing failure to metabolize 1,25-dihydroxyvitamin D.
    No preview · Article · Jan 2014 · The Journal of Clinical Endocrinology and Metabolism
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    ABSTRACT: Bioactivation of vitamin D consists of two sequential hydroxylation steps to produce 1α,25-dihydroxyvitamin D3. It is clear that the second or 1α-hydroxylation step is carried out by a single enzyme, 25-hydroxyvitamin D 1α-hydroxylase CYP27B1. However, it is not certain what enzyme or enzymes are responsible for the initial 25-hydroxylation. An excellent case has been made for vitamin D 25-hydroxylase CYP2R1, but this hypothesis has not yet been tested. We have now produced Cyp2r1(-/-) mice. These mice had greater than 50% reduction in serum 25-hydroxyvitamin D3. Curiously, the 1α,25-dihydroxyvitamin D3 level in the serum remained unchanged. These mice presented no health issues. A double knockout of Cyp2r1 and Cyp27a1 maintained a similar circulating level of 25-hydroxyvitamin D3 and 1α,25-dihydroxyvitamin D3. Our results support the idea that the CYP2R1 is the major enzyme responsible for 25-hydroxylation of vitamin D, but clearly a second, as-yet unknown, enzyme is another contributor to this important step in vitamin D activation.
    Preview · Article · Sep 2013 · Proceedings of the National Academy of Sciences
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    ABSTRACT: In 2011, the US Institute of Medicine updated the definition of vitamin D inadequacy to serum 25-hydroxyvitamin D (25(OH)D) concentration of 30-<50 nmol/l and of deficiency to serum 25(OH)D < 30 nmol/l. We describe the prevalence of these conditions according to these definitions, seasonal variation in 25(OH)D and predictors of serum 25(OH)D concentrations among working, white women. Participants recorded lifestyle factors and dietary intake and provided fasting blood samples for measurement of serum 25(OH)D in both summer and winter. Predictors of serum 25(OH)D variation were analysed using linear regression and generalized linear mixed models. Kingston General Hospital in Kingston, Ontario, Canada, from April 2008 to July 2009. Female premenopausal nurses (n 83) working full-time rotating shifts. Deficient or inadequate vitamin D status was observed in 9 % of participants following summer/autumn and in 13 % following winter/spring. Predictors of serum 25(OH)D concentration were vitamin D supplement use, tanning bed use and season. Tanning bed use increased serum 25(OH)D by 23·24 nmol/l (95 % CI 8·78, 37·69 nmol/l, P = 0·002) on average. According to the 2011 Institute of Medicine bone health guidelines, over 10 % of nurses had deficient or inadequate vitamin D status following winter. Higher serum concentrations were associated with use of tanning beds and vitamin D supplements. As health promotion campaigns and legal restrictions are successful in reducing tanning bed use among women, our data suggest that increased prevalence of vitamin D inadequacy and deficiency may be a consequence, and that low vitamin D status will need to be countered with supplementation.
    Full-text · Article · Jul 2013 · Public Health Nutrition
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    ABSTRACT: Vitamin D supplementation in infancy is required to support healthy bone mineral accretion. A supplement of 400 IU of vitamin D per day is thought to support plasma 25-hydroxyvitamin D (25[OH]D) concentrations between 40 and 50 nmol/L; some advocate 75 to 150 nmol/L for bone health. To investigate the efficacy of different dosages of vitamin D in supporting 25(OH)D concentrations in infants. Double-blind randomized clinical trial conducted among 132 one-month-old healthy, term, breastfed infants from Montréal, Québec, Canada, between March 2007 and August 2010. Infants were followed up for 11 months ending August 2011 (74% completed study). Participants were randomly assigned to receive oral cholecalciferol (vitamin D3) supplements of 400 IU/d (n=39), 800 IU/d (n=39), 1200 IU/d (n=38), or 1600 IU/d (n=16). MAIN OUTCOMES AND MEASURES: The primary outcome was a plasma 25(OH)D concentration of 75 nmol/L or greater in 97.5% of infants at 3 months. Secondary outcomes included 25(OH)D concentrations of 75 nmol/L or greater in 97.5% of infants at 6, 9, and 12 months; 25(OH)D concentrations of 50 nmol/L or greater across all times; growth; and whole body and regional bone mineral content. Data were analyzed by intention to treat using available data, logistic regression, and mixed-model analysis of variance. By 3 months, 55% (95% CI, 38%-72%) of infants in the 400-IU/d group achieved a 25(OH)D concentration of 75 nmol/L or greater vs 81%(95% CI, 65%-91%) in the 800-IU/d group, 92% (95% CI, 77%-98%) in the 1200-IU/d group, and 100% in the 1600-IU/d group. This concentration was not sustained in 97.5% of infants at 12 months in any of the groups. The 1600-IU/d dosage was discontinued prematurely because of elevated plasma 25(OH)D concentrations. All dosages established 25(OH)D concentrations of 50 nmol/L or greater in 97% (95% CI, 94%-100%) of infants at 3 months and sustained this in 98% (95% CI, 94%-100%) to 12 months. Growth and bone mineral content did not differ by dosage. Among healthy, term, breastfed infants, only a vitamin D supplement dosage of 1600 IU/d (but not dosages of 400, 800, or 1200 IU/d) increased plasma 25(OH)D concentration to 75 nmol/L or greater in 97.5% of infants at 3 months. However, this dosage increased 25(OH)D concentrations to levels that have been associated with hypercalcemia. Identifier: NCT00381914.
    Full-text · Article · May 2013 · JAMA The Journal of the American Medical Association

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  • 1987-2015
    • Queen's University
      • • Department of Biomedical and Molecular Sciences
      • • Department of Biochemistry
      • • Department of Medicine
      Kingston, Ontario, Canada
  • 1990-2014
    • Queens University of Charlotte
      New York, United States
  • 2010
    • University of South Wales
      Понтиприте, Wales, United Kingdom