scholarly journals Urinary Vitamin D-Binding Protein as a Biomarker of Steroid-Resistant Nephrotic Syndrome

2016 ◽  
Vol 11 ◽  
pp. BMI.S31633 ◽  
Author(s):  
Michael R. Bennett ◽  
Angad Pordal ◽  
Christopher Haffner ◽  
LaTawnya Pleasant ◽  
Qing Ma ◽  
...  
Keyword(s):  
Vitamin D ◽  
Nephrotic Syndrome ◽  
Binding Protein ◽  
Area Under The Curve ◽  
Vitamin D Binding Protein ◽  
Cross Sectional ◽  
Steroid Resistant ◽  
Steroid Resistant Nephrotic Syndrome ◽  
Urine Creatinine ◽  
Normal Controls

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.

scholarly journals Influence of vitamin D binding protein polymorphism, demographics and lifestyle factors on vitamin D status of healthy Malaysian pregnant women

2020 ◽  
Author(s):  
Siew-Siew Lee ◽  
King-Hwa Ling ◽  
Maiza Tusimin ◽  
Raman Subramaniam ◽  
Kartini Farah Rahim ◽  
...  
Keyword(s):  
Vitamin D ◽  
Gene Polymorphism ◽  
Pregnant Women ◽  
Binding Protein ◽  
Lifestyle Factors ◽  
Vitamin D Supplementation ◽  
Dietary Vitamin ◽  
Vitamin D Binding Protein ◽  
Significant Positive Association ◽  
Cross Sectional

Abstract Background: Vitamin D deficiency (VDD) has been related to vitamin D binding protein (GC) gene polymorphism, demographics and lifestyle factors in different populations. However, previous studies only focused on demographic and lifestyle factors or genetic factors alone. Therefore, this cross-sectional study aimed to assess the association between GC gene polymorphism, demographics and lifestyle factors with VDD among Malaysian pregnant women. Method: Information on demographic characteristics, dietary vitamin D intake from supplement and food, time spent outdoors, skin type and clothing were collected using questionnaire. Plasma total 25-hydroxyvitamin D (25OHD) levels were measured using a Ultra-High-Performance Chromatography (UHPLC). Maternal GC single nucleotide polymorphisms (SNPs) (rs4588 and rs7041) were determined using restriction fragment length polymorphism (RFLP) technique. Results: Results showed that 50.2% of pregnant women were vitamin D deficient (25OHD <30 nmol/L). VDD (25OHD <30 nmol/L) was significantly associated with age, veiled clothing, maternal vitamin D intakes, from both food and supplements, and GC rs7041(and GC diplotypes). In contrast to previous studies that reported for non-pregnant population, significant positive association was found between CC genotype for SNP GC rs7041, GC 1s-1s and GC If-2 with risk of VDD (25OHD <30 nmol/L). Conclusions: The high prevalence of maternal VDD found in this study suggests the need for urgent development and implementation of vitamin D supplementation or fortification strategies to reduce VDD among pregnant women. The discrepancy in the association between GC rs7041 gene polymorphism and VDD reflects the variation in the factors associated with VDD in pregnancy compared to non-pregnant state

scholarly journals Polymorphism in Vitamin D-Binding Protein as a Genetic Risk Factor in the Pathogenesis of Endometriosis

2010 ◽  
Vol 31 (6) ◽  
pp. 943-944
Author(s):  
Klaus Faserl ◽  
Georg Golderer ◽  
Leopold Kremser ◽  
Herbert Lindner ◽  
Bettina Sarg ◽  
...  
Keyword(s):  
Vitamin D ◽  
Risk Factor ◽  
Acute Phase Proteins ◽  
Binding Protein ◽  
Medical Center ◽  
Cross Sectional Study ◽  
Vitamin D Binding Protein ◽  
Complement Components ◽  
Cross Sectional ◽  
Significant Difference

Context Previous studies have implicated a deficiency in the inflammatory response in women who develop endometriosis. The specific immunological deficits have not been completely elucidated. Objective Our objective was to identify differences in protein expression in serum that might shed light on the pathophysiology of endometriosis. Design and Setting This cross-sectional study of women undergoing laparoscopy between 2003 and 2005 took place at a university medical center. Patients Patients included consenting women age 18-49 yr undergoing surgery for pain and/or infertility or elective tubal ligation. Women with acute or chronic medical conditions were excluded. Intervention Blood was collected preoperatively. Main Outcome Measure Proteomic analysis of serum was done using two-dimensional difference gel electrophoresis. Results We found 25 protein spots with a significant difference in abundance between women with endometriosis and controls, including acute-phase proteins and complement components. The abundance of vitamin D-binding protein was higher in all endometriosis pools by a factor of approximately 3 compared with the control pool (P &lt; 0.02). Analysis of specific allele products using nano-LC-ESI-MS indicated that it was the GC*2 allele product that was in greater concentration in serum pools, as well as in single validation samples, in women with endometriosis (P = 0.006). In contrast to the GC*1 allele product, which is readily converted to a potent macrophage factor (Gc protein-derived macrophage-activating factor), the GC*2 allele product undergoes practically no such conversion. Conclusions We speculate that the inability to sufficiently activate macrophages’ phagocytotic function in those carrying the GC*2 polymorphism (more prevalent in endometriosis) may allow endometriotic tissues to implant in the peritoneal cavity. Future studies evaluating specific vitamin D-binding protein polymorphisms as a risk factor for endometriosis in larger populations of women are warranted.

scholarly journals Vitamin D-Binding Protein Clearance Ratio Is Significantly Associated with Glycemic Status and Diabetes Complications in a Predominantly Vitamin D-Deficient Population

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Nabila A. Abdella ◽  
Olusegun A. Mojiminiyi
Keyword(s):  
Vitamin D ◽  
Cell Function ◽  
Binding Protein ◽  
Area Under The Curve ◽  
Significant Negative Correlation ◽  
Receiver Operating Curve ◽  
Tubular Damage ◽  
Vitamin D Binding Protein ◽  
Glycemic Status ◽  
Clearance Ratio

Introduction. Studies have shown increased urine excretion of vitamin D-binding protein (VDBP) in patients with diabetic nephropathy (DN) resulting from postulated mechanisms linked to renal tubular damage. In this study, we evaluate the utility of VDBP clearance ratio as a novel determinant of glycemic status, DN, and other diabetes-associated complications.Methods. Levels of vitamin D, HbA1c, serum, urine concentrations of VDBP, and creatinine were measured in 309 subjects. The ratio of urine microalbumin to creatinine was determined to categorize subjects as normoalbuminuric (NAO), microalbuminuric (MIA), and macroalbuminuric (MAA). The VDBP clearance ratio was calculated.Results. Mean VDBP clearance ratios in NAO, MIA, and MAA were 0.7, 4, and 15, respectively. Significant positive correlations of VDBP clearance ratio were found with age, WC, SBP, DBP, TG, glucose, HbA1c, urine VDBP, urine microalbumin, and urine microalbumin/creatinine, and a significant negative correlation was found with the steady-state estimate of beta cell function (B%). Receiver operating curve (ROC) analyses of the use of VDBP clearance ratio for detection of albumin status shows a value of 0.81 for the area under the curve.Conclusions. The strong associations of VDBP clearance ratio with glycemic control and diabetes-associated complications suggest that this index could play a wider role in detection and/or pathogenesis and complications of diabetes.

scholarly journals Influence of vitamin D binding protein polymorphism, demographics and lifestyle factors on vitamin D status of healthy Malaysian pregnant women

2020 ◽  
Author(s):  
Siew-Siew Lee ◽  
King-Hwa Ling ◽  
Maiza Tusimin ◽  
Raman Subramaniam ◽  
Kartini Farah Rahim ◽  
...  
Keyword(s):  
Vitamin D ◽  
Gene Polymorphism ◽  
Pregnant Women ◽  
Binding Protein ◽  
Lifestyle Factors ◽  
Vitamin D Supplementation ◽  
Dietary Vitamin ◽  
Vitamin D Binding Protein ◽  
Significant Positive Association ◽  
Cross Sectional

Abstract Background: Vitamin D deficiency (VDD) has been related to vitamin D binding protein (GC) gene polymorphism, demographics and lifestyle factors in different populations. However, previous studies only focused on demographic and lifestyle factors or genetic factors alone. Therefore, this cross-sectional study aimed to assess the association between GC gene polymorphism, demographics and lifestyle factors with VDD among Malaysian pregnant women.Method: Information on demographic characteristics, dietary vitamin D intake from supplement and food, time spent outdoors, skin type and clothing were collected using questionnaire. Plasma total 25-hydroxyvitamin D (25OHD) levels were measured using a Ultra-High-Performance Chromatography (UHPLC). Maternal GC single nucleotide polymorphisms (SNPs) (rs4588 and rs7041) were determined using restriction fragment length polymorphism (RFLP) technique.Results: Results showed that 50.2% of pregnant women were vitamin D deficient (25OHD <30 nmol/L). VDD (25OHD <30 nmol/L) was significantly associated with age, veiled clothing, maternal vitamin D intakes, from both food and supplements, and GC rs7041(and GC diplotypes). In contrast to previous studies that reported for non-pregnant population, significant positive association was found between CC genotype for SNP GC rs7041, GC 1s-1s and GC If-2 with risk of VDD (25OHD <30 nmol/L). Conclusions: The high prevalence of maternal VDD found in this study suggests the need for urgent development and implementation of vitamin D supplementation or fortification strategies to reduce VDD among pregnant women. The discrepancy in the association between GC rs7041 gene polymorphism and VDD reflects the variation in the factors associated with VDD in pregnancy compared to non-pregnant state

scholarly journals Vitamin D-Binding Protein (Gc-Globulin) in Acute Liver Failure in Children

Diagnostics ◽  
2020 ◽  
Vol 10 (5) ◽  
pp. 278
Author(s):  
Alina Grama ◽  
Lucia Burac ◽  
Cornel Olimpiu Aldea ◽  
Bogdan Bulata ◽  
Dan Delean ◽  
...  
Keyword(s):  
Vitamin D ◽  
Liver Failure ◽  
Acute Liver Failure ◽  
Binding Protein ◽  
Area Under The Curve ◽  
Serum Levels ◽  
Control Group ◽  
Vitamin D Binding Protein ◽  
Disease Outcomes ◽  
Poor Outcomes

This study aimed to analyse vitamin D-binding protein (Gc-globulin) serum levels in acute liver failure (ALF) in children in relation to disease outcomes and correlations with other known markers used to evaluate the severity of ALF. Our study included 34 children (mean age 4.87 ± 5.30 years) with ALF of different causes (metabolic, 26.47%; autoimmune, 23.53%; toxic, 20.59%; infection, 17.65%; unknown, 11.76%) and 30 children without any liver injury (mean age 6.11 ± 4.26 years). The outcome was poor in 14 patients (41.18%), including one child with liver transplantation (2.94%). Serum Gc-globulin levels were significantly lower in ALF patients compared to the control group (151.57 ± 171.8 mg/L vs. 498.63 ± 252.50 mg/L; p < 0.000001), with an optimum cut-off of 163.5 mg/L (Area Under the Curve, AUC, 0.8921; sensitivity, 76.50%; specificity, 100%). Levels were also lower in patients with poor outcomes compared to survivors (59.34 ± 33.73 mg/L vs. 216.12 ± 199.69 mg/L; p < 0.0001), with an optimum cut-off 115 mg/L (AUC, 0.7642; sensitivity, 100%; specificity, 50%). Gc-globulin serum levels were variable according to ALF aetiology, i.e., lower in metabolic, infectious, or unknown causes compared to autoimmune and toxic causes. Gc-globulin serum levels were decreased in children with ALF and lower in those with poor outcomes compared with survivors. Gc-globulin serum levels were correlated with other known parameters used to evaluate the severity of ALF and could help to identify patients at high risk for poor outcomes.

scholarly journals The Isoform GC1f of the Vitamin D Binding Protein Is Associated with Bronchiectasis Severity

Biomedicines ◽  
2021 ◽  
Vol 9 (11) ◽  
pp. 1573
Author(s):  
Martina Oriano ◽  
Stefano Aliberti ◽  
Franca Rosa Guerini ◽  
Cristina Agliardi ◽  
Carlotta Di Francesco ◽  
...  
Keyword(s):  
Vitamin D ◽  
Binding Protein ◽  
Severe Disease ◽  
Cross Sectional Study ◽  
Nucleotide Polymorphisms ◽  
Vitamin D Binding Protein ◽  
Coding Region ◽  
Chronic Infections ◽  
Cross Sectional ◽  
Vitamin D Levels

Vitamin D modulates immune responses and its deficiency has been observed in more than 60% of bronchiectasis patients. Vitamin D binding protein (DBP) is coded by the GC gene, is involved in the transport of vitamin D, and includes a number of isoforms based on single nucleotide polymorphisms (SNPs) in the coding region at rs7041 and rs4855. We evaluated the possible clinical impact of DBP polymorphisms and isoforms in an observational, cross-sectional study conducted in 116 bronchiectasis patients, who were genetically characterized for rs4588 and rs7041 SNPs. Results showed that the GC1f isoform (rs7041/rs4588 A/G) correlated with a more severe disease (18.9% vs. 6.3%, p = 0.038), a higher incidence of chronic infections (63.6% vs. 42%, p = 0.041), and a lower BACI score (0.0 (0.0, 2.5) vs. 3.0 (0.0, 3.0), p = 0.035). Moreover, blood concentration of vitamin D was higher in patients carrying GC1s (median (IQR): 20.5 (14.3, 29.7 vs. 15.8 (7.6, 22.4), p = 0.037). Patients carrying GC1f isoform have a more severe disease, more chronic infections and lower asthmatic comorbidity in comparison to those without the GC1f isoform. Presence of the GC1s isoform (rs7041/rs4588 C/G) seems to be associated to a milder clinical phenotype with increased vitamin D levels and lower comorbidities score.

Comparison of urinary vitamin D binding protein with albumin-creatinine ratio in type 2 Diabetes Mellitus as an early screening tool for diabetic nephropathy

2020 ◽  
Vol 13 (4) ◽  
pp. 170-174
Author(s):  
Hafiz Muhammad Khalid Mehmood ◽  
Munazza Yasmeen ◽  
Sumbla Ghaznavi ◽  
Mr. Abdul Waheed ◽  
Miss Nadia Rasheed
Keyword(s):  
Diabetes Mellitus ◽  
Vitamin D ◽  
Diabetic Nephropathy ◽  
Early Detection ◽  
Urine Sample ◽  
Binding Protein ◽  
Creatinine Ratio ◽  
Vitamin D Binding Protein ◽  
Urine Creatinine ◽  
Current Diagnostic Criterion

ABSTRACT   Introduction:- Diabetes mellitus (DM) is a group of metabolic disorders. Diabetic nephropathy is one of the chronic complications of DM, leading to End stage renal disease (ESRD). A current diagnostic criterion for diabetic nephropathy is measurement of microalbuminuria, which is 30 to 300 mg of albumin/24 hour’s urine or ratio of albumin to creatinine  (ACR) in the range of 30 to 300 mg/g in random urine sample but it shows inadequate sensitivity for the early detection of diabetic nephropathy. Methodology:- This was a comparative cross sectional study, which comprised of seventy five study subjects and were distributed into three study groups with 25 subjects in each group, having age  in the range of 40-50 years.Group-1 comprising controls (without diabetes mellitus),Group-2 contained diabetes mellitus patients with normoalbuminuria. Group-3 composed of diabetes mellitus patients with microalbuminuria. Vitamin D binding protein, urine creatinine and albumin was measured from the urine sample of each study subjects. Determination of creatinine in urine was performed by jaffe method and albumin in urine was determined by immunoturbidimetric method. Vitamin D binding protein was measured by ELISA method. Levels of VDBP and albumin were normalized with urine creatinine and expressed as VDBP creatinine ratio as (ng/mg) and albumin creatinine ratio as (mg/g) in the spot urine sample. Results:-Results of this study showed that level of Vitamin D binding protein was significantly increased in diabetes mellitus in comparison to control subjects. Conclusion:- Our results proposes that urinary vitamin D binding protein levels is likely to become a useful biomarker for the early detection of diabetic nephropathy in diabetic patients which can be helpful in early treatment and will help to manage diabetic nephropathy. ABSTRACT Introduction: Diabetes mellitus (DM) is a group of metabolic disorders. Diabetic nephropathy is one of the chronic complications of DM, leading to end stage renal disease (ESRD). A current diagnostic criterion for diabetic nephropathy is measurement of microalbuminuria, which is 30 to 300 mg of albumin/24 hour’s urine or ratio of albumin to creatinine (ACR) in the range of 30 to 300 mg/g in random urine sample but it shows inadequate sensitivity for the early detection of diabetic nephropathy .Current diagnostic criterion for diabetic nephropathy (DN) is detection of microalbuminuria, which is 30 – 300 mg/24 hours of albumin excretion in urine or albumin to creatinine ratio (ACR) in the range of 30 – 300 mg/g in the random urine sample but, it shows inadequate sensitivity for the early detection of DN. It has been observed that increased excretion of UVDBP is related to tubular dysfunction. This protein is excreted in urine earlier than albumin. Hence it can be used as a tool to early detection of DN in type 2 diabetic patients. Methodology: This was a comparative cross sectional study, which comprised of seventy five study subjects and were distributed into three study groups with 25 subjects in each group, having age in the range of 40-50 years. Group-1 comprising controls (without diabetes mellitus), Group-2 had diabetes mellitus with normoalbuminuria while Group-3 comprised of diabetes mellitus patients with microalbuminuria. Vitamin D binding protein, urine creatinine and albumin were measured from the random urine sample preferably early in the morning urine sample of each study subjects using ELISA, Jaffe and immunoturbidimetric methods respectively. Levels of VDBP and albumin were normalized with urine creatinine and expressed as VDBP creatinine ratio as (ng/mg) and albumin creatinine ratio as (mg/g) in the spot urine sample. Results: Urinary VDBP levels among the three groups were as the highest Median, IQR (Q1- Q3) values were observed in group 3 as 1056 ng/mg,(905 ng/mg – 1215 ng/mg) followed by group 2 as 442 ng/mg,(381.50 ng/mg – 523 ng/mg) and group 1 as 98 ng/mg,(73.50 ng/mg – 149 ng/mg) respectively, and a statistical significant difference was observed among the three groups with a p- value of 0.000. Results of this study showed that level of Vitamin D binding protein was significantly increased in diabetes mellitus in comparison to control subjects. Conclusion: Results suggest that urinary vitamin D binding protein level is likely to become a useful biomarker for the early detection and management of diabetic nephropathy in Type 2 diabetic patients.  

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