Studies on vitamin D binding protein in the nephrotic syndrome.

1985 ◽  
Vol 31 (5) ◽  
pp. 718-721 ◽  
Author(s):  
K Colston ◽  
N J Williams ◽  
H J Cleeve

Abstract We studied the properties of vitamin D binding protein in plasma and urine from nine patients with nephrotic syndrome. Samples were incubated with 25-[3H]hydroxyvitamin D3, after which we determined binding capacity and apparent dissociation constants. Binding capacity was markedly less in plasma from patients with nephrotic syndrome than that from normal subjects, but binding affinity was unchanged. Specific binding of 25-hydroxy[3H]vitamin D3 could be demonstrated in urine from all the nephrotic patients, and sucrose density-gradient analysis of these urines revealed a single binding peak with sedimentation characteristics similar to those of vitamin D binding protein in plasma.

2011 ◽  
Vol 38 (10) ◽  
pp. 2224-2229 ◽  
Author(s):  
KYONG-HEE JUNG ◽  
TAE-HWAN KIM ◽  
DONG-HYUK SHEEN ◽  
MI-KYOUNG LIM ◽  
SANG-KWANG LEE ◽  
...  

Objective.Genetic factors account for more than 90% of overall susceptibility to ankylosing spondylitis (AS), and recent studies have focused on non-major histocompatibility complex genes. Vitamin D binding protein (DBP) is a highly polymorphic protein that transports vitamin D and its metabolites. In addition to its sterol binding capacity, DBP has many other roles in the inflammatory and immune systems, and has been reported to be associated with autoimmune diseases. We investigated the association between DBP polymorphisms and susceptibility to AS.Methods.This case-control study was conducted in 223 patients with AS and 239 ethnically matched controls who were genotyped for 8 single-nucleotide polymorphisms (SNP) in the DBP and its promoter. Genomic DNA was isolated from peripheral blood leukocytes using the standard phenolchloroform method, and the GoldenGate assay was used for genotyping.Results.No significant association was found between the susceptibility to AS and DBP polymorphisms. In a subgroup analysis of patients with AS, G alleles at rs222016 and rs222020 (OR 0.63, 95% CI 0.42–0.95, p = 0.03; OR 0.63, 95% CI 0.42–0.95, p = 0.03, respectively) and A allele at rs3733359 (OR 0.59, 95% CI 0.39–0.90, p = 0.01) showed the decreased risk of peripheral arthritis. G allele at rs4752 showed increased risk of uveitis (OR 2.04, 95% CI 1.12–3.72, p = 0.02). On the haplotype analyses, haplotype 2 (AGGA) protected against the development of peripheral arthritis (p = 0.01) and haplotype 3 (GAAG) was associated with an increased likelihood of uveitis (p = 0.02).Conclusion.DBP gene polymorphisms are associated with the development of peripheral arthritis and uveitis in Korean patients with AS. Given the influence of different DBP variants on the immune system, larger-scale studies are warranted to elucidate the role of DBP in the pathogenesis of AS.


1990 ◽  
Vol 68 (10) ◽  
pp. 1368-1371 ◽  
Author(s):  
Reinhold Vieth ◽  
Matt J. Kessler ◽  
Kenneth P. H. Pritzker

The specific binding of 25-hydroxyvitamin D3 to its binding protein was studied in serum of the human, rhesus monkey, cow, horse, and rat. The free fraction of 25-hydroxyvitamin D3 in the rat was 0.34 ± 0.15 pmol free/nmol total (±SD) and this was lower than in any of the other species (p < 0.01). In the human, the free fraction was 1.5 ± 0.32 pmol free/nmol total, which was higher than in any of the other species (p < 0.001). The differences in the free fraction were mainly due to differences in dissociation constant. The relative levels of free 25-hydroxyvitamin D should be taken into account when extrapolating findings about vitamin D metabolism in animals to the human. A technical outcome of this study is that of the species tested, vitamin D binding protein from rat serum is the most suitable as a reagent component for methods used to measure total 25-hydroxyvitamin D by competitive protein binding assay.Key words: vitamin D binding protein, 25-hydroxyvitamin D, free metabolite, species comparison.


2016 ◽  
Vol 11 ◽  
pp. BMI.S31633 ◽  
Author(s):  
Michael R. Bennett ◽  
Angad Pordal ◽  
Christopher Haffner ◽  
LaTawnya Pleasant ◽  
Qing Ma ◽  
...  

Background Idiopathic nephrotic syndrome (NS) is one of the most common glomerular disorders of childhood and is associated with increased urinary vitamin D-binding protein (uVDBP) excretion. We tested the hypothesis that uVDBP represents a biomarker to differentiate steroid-resistant nephrotic syndrome (SRNS) from the more benign forms of steroid-sensitive nephrotic syndrome (SSNS). Methods This cross-sectional study included children with SRNS ( n = 24), SSNS ( n = 28), and normal controls ( n = 5). Urine and clinical data were collected from patients. Measurements of uVDBP were performed with a commercially available ELISA kit and normalized to urine creatinine. Results Concentrations of uVDBP were significantly higher ( P < 0.001) in patients with SRNS (13,659 ng/mL, interquartile range [IQR] 477–22,979) than in patients with SSNS (94 ng/mL, IQR 53–202) and normal controls (23 ng/mL, IQR 22–99, P = 0.002). Significance did not change when the results were corrected for urine creatinine. uVDBP was significantly negatively correlated with estimated glomerular filtration rate (eGFR; R = −0.76, P = 0.03). However, uVDBP was still markedly elevated in patients with SRNS with eGFR >100 mL/minute/1.73 m2. There was a positive correlation between microalbuminuria (MALB/Cr) and uVDBP ( R = 0.67, P < 0.001). However, uVDBP displayed a much higher discriminatory ability for distinguishing SRNS than MALB/Cr (area under the curve = 0.92 vs 0.67, respectively). An uVDBP cutoff of 362 ng/mL yielded the optimal sensitivity (80%) and specificity (83%) to distinguish SRNS from SSNS. Conclusions In this preliminary study, uVDBP represents a noninvasive biomarker that could distinguish SRNS from the more benign SSNS with high discriminatory power.


1992 ◽  
Vol 38 (9) ◽  
pp. 1796-1801 ◽  
Author(s):  
M A Haughton ◽  
R S Mason

Abstract An automated immunonephelometric assay was developed to measure vitamin D-binding protein (DBP) in serum. The assay is described for the Behring Nephelometer System, which uses rabbit anti-DBP antiserum and purified human DBP. The detection limit is 0.05 g/L (0.86 mumol/L), and the working range is less than or equal to 1.60 g/L (27.59 mumol/L). Intra- and interassay CVs of 2.0% and 2.8-3.8% compare favorably with alternative methods. When results were compared with those from a immunoradiometric assay, the correlation coefficient was 0.976 (P less than 0.001), and the regression equation [y = 0.866 +/- 0.085x + 0.05 (Syx = 0.042, n = 42)] identified a negative bias. Analysis indicated that both methods appeared to contribute equally to the bias. Although the assay was relatively free from analytical interference, falsely increased values were noted in severely lipemic specimens and in frozen specimens. Interference may be minimized by inclusion of Supplementary Precipitation reagent in a modified assay protocol. The range of concentrations expected in clinical samples was established from normal subjects [0.32-0.46 g/L (5.52-7.93 mumol/L), n = 28], pregnant subjects [0.51-0.70 g/L (8.79-12.07 mumol/L), n = 13], and subjects with liver diseases [0.12-0.33 g/L (2.07-5.69 mumol/L), n = 18].


1987 ◽  
Vol 22 (4) ◽  
pp. 259-263 ◽  
Author(s):  
Joe W. Krayer ◽  
David L. Emerson ◽  
Pascal J. Goldschmidt-Clermont ◽  
Andre E. Nel ◽  
Philip A. Werner ◽  
...  

2017 ◽  
Vol 6 (2) ◽  
pp. 111-120 ◽  
Author(s):  
Göran Oleröd ◽  
Lillemor Mattsson Hultén ◽  
Ola Hammarsten ◽  
Eva Klingberg

Purpose Serum 25-hydroxy vitamin D [25(OH)D] varies greatly with season at northern latitudes. The purpose of this study was to determine if the seasonal variations in serum total 25(OH)D are followed by a concomitant variation in free 25(OH)D or if the variation is damped by alterations in the binding capacity of DBP. Methods Serum was collected from 540 healthy blood donors (60% men; mean age 41 ± 13 years) during 12 months and analyzed for total 25(OH)D, directly measured free 25(OH)D, vitamin D-binding protein (DBP) and albumin. Calculated free 25(OH)D was estimated. Results The UV-B radiation during the sampling month was positively correlated with the serum levels of total 25(OH)D (r = 0.355, P < 0.001), directly measured free (r = 0.336, P < 0.001) and calculated free 25(OH)D (r = 0.275, P < 0.001), but not with DBP and albumin. The percentage of free 25(OH)D was higher during the winter months than that during the summer months (0.020 ± 0.005% vs 0.019 ± 0.004%; P = 0.007) and higher in participants with a serum 25(OH)D below 25 nmol/L than that in participants with a serum 25(OH)D above 75 nmol/L (0.031 ± 0.007% vs 0.017 ± 0.003%; P < 0.001). iPTH was correlated with directly measured free 25(OH)D (r = −0.226; P < 0.001), but only weakly with calculated free 25(OH)D (r = −0.095; P = 0.027). Conclusions Directly measured free serum 25(OH)D was highly correlated with total serum 25(OH)D and followed the same seasonal variation, whereas the serum concentrations of DBP and albumin were stable. The fluctuation in free 25(OH)D was only marginally damped with an increase in the percentage of free 25(OH)D during the winter months and in participants with vitamin D deficiency.


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