D-binding Protein Levels Research Articles

Indian ASD probands with 25(OH)D and vitamin D binding protein deficiency exhibited higher severity

The severity of autism spectrum disorder (ASD) shows wide variations, though the reason remains unclear. Vitamin D (VitD) deficiency is considered a risk factor for ASD and its supplementation was reported to reduce symptom severity. Since VitD, either synthesized in the skin or absorbed from the food, is transported to the liver by the vitamin D binding protein (DBP), we have analyzed DBP genetic polymorphisms [rs7041 (A/C), rs4588 (G/T), and rs3755967 (C/T)] affecting DBP function [Case = 411; Control = 397], levels of plasma 25(OH)D and DBP [Case = 25; Control = 26], and DBP mRNA expression [Case = 74; Control = 44] in a group of Indo-Caucasoid ASD probands and neurotypical subjects. ASD probands with rs7041’CC’, rs4588 ‘TT’, and rs3755967 ‘TT’ genotypes exhibited higher scores for a few traits. Scores for Imitation and Listening response were also higher in the presence of the “A-T” haplotype (rs7041–rs4588). Plasma 25(OH)D and DBP levels as well as DBP mRNA expressions were significantly lower in the ASD probands as compared to the neurotypical subjects. We infer that DBP deficiency, in the presence of risk genetic variants, could be one of the reasons for the reported 25(OH)D deficiency of the ASD probands.

The Effect of Phototherapy on Systemic Inflammation Measured with Serum Vitamin D-Binding Protein and hsCRP in Patients with Inflammatory Skin Disease.

Vitamin D plays a role in inflammatory skin disease, but the exact mechanisms and the clinical significance remain unclear. According to the free hormone hypothesis, it is the free concentration of 25-hydroxy vitamin D (25(OH)D) that is biologically active. Vitamin D-binding protein (DBP) acts as the major transporter of vitamin D in the circulation, and DBP concentration defines the free 25(OH)D levels. DBP levels are elevated in various inflammatory conditions, including psoriasis. Narrowband-ultraviolet B (NB-UVB) is the most widely used phototherapy and is an established first-line treatment for psoriasis and atopic dermatitis (AD), often used before proceeding to systemic treatment. The aim of this study was to investigate the influence of NB-UVB phototherapy on DBP and high-sensitivity C-reactive protein (hsCRP) levels, as markers of systemic inflammation, in inflammatory skin disease. Thirty adults (psoriasis (n = 20) and AD (n = 10)) were treated with NB-UVB. Serum DBP, hsCRP, total and free 25(OH)D, and 1,25-dihydroxy vitamin D (1,25(OH)2D) were measured before and after NB-UVB. Disease severity was assessed with Psoriasis Area and Severity Index (PASI), SCORing Atopic Dermatitis (SCORAD), and Visual Analogue Scale (VAS). DBP decreased in psoriasis patients and varied with no clear trend in AD patients. HsCRP decreased in both groups, but this did not reach statistical significance. PASI, SCORAD, and VAS improved, and vitamin D levels increased after NB-UVB. Sub-analysis indicated a better response to NB-UVB for patients with vitamin D deficiency and insufficiency compared to vitamin D-sufficient patients. The decrease in DBP after NB-UVB in psoriasis patients suggests a potential systemic anti-inflammatory effect of phototherapy. Measurement of vitamin D levels may potentially serve as a tool to identify patients who would derive the greatest benefit from NB-UVB phototherapy.

Effect of vitamin D binding protein gene polymorphism on susceptibility and prognosis of severe acute pancreatitis

To investigate the effect of vitamin D binding protein (DBP) gene polymorphism on susceptibility and prognosis of severe acute pancreatitis (SAP). A prospective study was conducted. Eighty-three patients with SAP who were admitted to the department of general surgery of Tianjin Fifth Central Hospital from March 2018 to March 2021 were selected as the research objects, and 83 healthy people in the same period were selected as controls. Peripheral blood RNA was extracted and reverse transcribed into cDNA, and the genotype and allele frequency of DBP gene rs7041 locus were detected by fluorescence quantitative analyzer. Hardy-Weinberg equilibrium was used to test the genetic balance. On the day of admission, serum C-reactive protein (CRP) level was detected by scattering immunoturbidimetry, serum procalcitonin (PCT) level was detected by electrochemiluminescence, serum DBP level was detected by enzyme-linked immunosorbent assay (ELISA), and neutrophil to lymphocyte ratio (NLR) was calculated automatically by the instrument. The length of intensive care unit (ICU) stay, the length of hospital stay and prognosis during hospitalization of patients were statistically analyzed. Multivariate Logistic regression analysis was used to screen the influencing factors of SAP occurrence. The results of Hardy-Weinberg equilibrium test showed that the distribution of gene polymorphisms in the two groups of subjects conformed to the law of genetic equilibrium. The frequencies of TT genotype and T allele of DBP gene rs7041 locus in the patients of SAP group were significantly higher than those in the healthy control group [TT genotype: 34.94% (29/83) vs. 9.64% (8/83), T allele: 55.42% (92/166) vs. 38.55% (64/166), both P < 0.01], and the frequency of GT genotype was significantly lower than that in the healthy control group [40.96% (34/83) vs. 57.83% (48/83), P < 0.05]. There was no significant difference in the frequency of GG genotype between the healthy control group and SAP group [32.53% (27/83) vs. 24.10% (20/83), P > 0.05]. Further multivariate Logistic regression analysis showed that TT genotype [odds ratio (OR) = 2.831, 95% confidence interval (95%CI) was 1.582-5.067, P < 0.001] and T allele (OR = 2.533, 95%CI was 1.435-4.472, P < 0.001) of DBP gene rs7041 locus were independent risk factors for SAP in healthy people, while GT genotype was a protective factor for SAP (OR = 0.353, 95%CI was 0.143-0.868, P = 0.041). The levels of CRP, PCT, NLR and DBP in patients with TT genotype of DBP gene rs7041 locus were significantly higher than those in patients with GG/GT genotype on the day of admission in SAP group [CRP (mg/L): 43.25±13.25 vs. 31.86±12.83, PCT (μg/L): 1.53±0.24 vs. 1.21±0.20, NLR: 3.15±0.53 vs. 2.71±0.48, DBP (μg/L): 87.78±19.64 vs. 70.58±18.67, all P < 0.01]. The length of ICU stay in patients with TT genotype of DBP gene rs7041 locus in SAP group was significantly longer than that in patients with GG/GT genotype (days: 11.35±1.58 vs. 9.71±1.35, P < 0.01). The length of hospital stay of patients with TT genotype was longer than that of patients with GG/GT genotype (days: 23.41±3.64 vs. 23.17±3.57), and the in-hospital mortality was higher than that of patients with GG/GT genotype [34.48% (10/29) vs. 29.63% (16/54)], but the difference was not statistically significant (both P > 0.05). The risk of SAP was significantly increased in patients with TT genotype of rs7041 locus of DBP gene, and the mechanism may be related to the increase of DBP expression. And carrying the TT genotype will prolong the ICU hospitalization time of SAP patients, but the effect on prognosis is not obvious.

Free vitamin D and vitamin D binding protein in multiple sclerosis patients

Objective: In multiple sclerosis (MS), where low vitamin D level is a risk factor, there is no previous study evaluating the level of free vitamin D by direct measurement, and there is little information about vitamin D binding protein (DBP). This study assessed free vitamin D and DBP in patients with MS. Methods: The study subjects consisted of 43 MS patients and 25 controls. Free vitamin D and DBP levels were measured through an enzyme-linked immunosorbent (ELISA) kit. Results: The patient group had a mean age of 36.58 ± 9.4 (19-60) and the control group had a mean age of 33.56 ± 9.65 (24-52) years (p=0.210). The patient had free vitamin D level of 21.51 ±9.72 pg/ml and the free vitamin D level of the control group was 26.02 ±9.29 pg/ml. Free vitamin D levels did not significantly differ across the groups (p=0.065). The patient group (34.78 ±18.24 ng/ml) had a significantly higher DBP level than the control group (15.36 ±10.64 ng/ml) (p&lt;0.001). Conclusion: MS patients have higher DBP than healthy control, while the free vitamin D levels of the patients tend to be lower.

Association of Blood Levels of Vitamin D and Its Binding Protein with Clinical Phenotypes of Multiple Sclerosis.

Low vitamin D levels may synergize with changing levels of the vitamin D binding protein (DBP) to precipitate in the development and clinical progression of multiple sclerosis (MS). In this study, this hypothesis was explored in groups of Kuwaiti healthy controls and patients with different clinical phenotypes of MS. Fasting serum concentrations of 25-hydroxyvitamin D [25(OH)D] and DBP were measured in 146 healthy controls and 195 patients with MS. The latter were classified according to the duration, type, and onset of the disease and the mode of treatment. Factors such as relapse/remitting, and the use of nutritional supplements were also considered. The DBP levels were significantly lower in the patients than in the controls. This was more evident in newly diagnosed drug-naïve patients than in those patients with more established MS. MS status and severity were negatively impacted by concurrently low levels of 25(OH)D and DBP. This was most clearly expressed in drug-naïve patients and in those with a disease in relapse. It was also established that the 25(OH)D level had a significant positive correlation with the duration of the disease. Lower levels of 25(OH)D and DBP appear to have a synergistic effect on MS status. This was most clearly demonstrated in patients who were newly diagnosed (drug-naïve) and in those patients who were in relapse.

Correlation of Plasma 25(OH)D3 and Vitamin D Binding Protein Levels with COVID-19 Severity and Outcome in Hospitalized Patients.

The Coronavirus Disease-19 (COVID-19) caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) has been declared a worldwide pandemic. The severity of COVID-19 varies greatly across infected individuals. Possible factors may include plasma levels of 25(OH)D and vitamin D binding protein (DBP), as both are involved in the host immune response. Other possible nutrition-related factors include malnutrition and/or obesity which disrupt the optimal host immune response to infections. Current literature shows inconsistent evidence about the association of plasma 25(OH)D3 and DBP on infection severity and clinical outcomes. This study aimed to measure plasma 25(OH)D3 and DBP in hospitalized COVID-19 cases and assess their correlation with infection severity, inflammatory markers, and clinical outcome. 167 patients were included in this analytical cross-sectional study, of which 81 were critical and 86 were non-critical hospitalized COVID-19 patients. Plasma levels of 25(OH)D3, DBP, and the inflammatory cytokines, IL-6, IL-8, IL-10, and TNF-α were assessed using the Enzyme-linked Immunosorbent Assay (ELISA). Information regarding biochemical and anthropometrical indices, hospital length of stay (LoS), and illness outcome was obtained from the medical records. Plasma 25(OH)D3 level was found to be significantly lower in critical compared to non-critical patients (Median = 8.38 (IQR = 2.33) vs. 9.83 (IQR = 3.03) nmol/L, respectively; p < 0.001), and it positively correlated with hospital LoS. However, plasma 25(OH)D3 did not correlate with mortality or any of the inflammatory markers. DBP on the other hand correlated positively with mortality (rs = 0.188, p = 0.015) and hospital LoS (rs = 0.233, p = 0.002). DBP was significantly higher in critical than non-critical patients (Median = 1262.18 (IQR = 463.66) vs. 1153.35 (IQR = 418.46) ng/mL, respectively; p < 0.001). Furthermore, IL-6 and IL-8 were significantly higher in critical than non-critical patients. However, no differences were found in IL-10, TNF-α, IL-10/TNF-α, TNF-α/IL-10, IL-6/IL-10, or CRP between groups. The current study found that critical COVID-19 patients had lower 25(OH)D3 than non-critical patients, yet, levels were found to be suboptimal in both groups. Further, critical patients had higher DBP levels as compared to non-critical patients. This finding may encourage future research to unravel the effects of this understudied protein that appears to have significant associations with inflammation, even though the precise mechanism is unknown.

The pathogenetic role of vitamin D and vitamin D-binding protein in the development of urinary tract infection in children

Background. The aim of the research was to study the content of 1,25(OH)2D3 and vitamin D-binding protein (DBP) in the blood serum of children with urinary tract infections, taking into account the clinical form of the disease, and to determine their pathogenetic role in the development of urinary tract infections. Materials and methods. The study groups consisted of 84 children (mean age — 10.0 ± 1.3 years). The main group was divided into subgroups: the first one — 17 children with acute pyelonephritis, the second one — 21 patients with chronic pyelonephritis, the third one — 16 children with acute cystitis, the fourth one — 10 patients with unspecified urinary tract infections. The control group consisted of 20 relatively healthy children. The content of 1,25(OH)2D3 and DBP was investigated by immunoenzymatic analysis. Results. It was found that the development of the inflammatory process in the urinary tract was accompanied by a statistically significant (p &lt; 0.01) decrease in the level of 1,25(OH)2D3 in the blood serum of the children of the main group compared to the controls. The level of 1,25(OH)2D3 in patients of all subgroups was significantly lower than that of the control group (p &lt; 0.01), but there was no statistical difference between them. Serum level of DBP in the main group was statistically significantly (p &lt; 0.05) increased compared to the controls, but we did not find a statistically significant difference between the subgroups studied. Conclusions. The development of an acute inflammatory process in the urinary tract in children occurs against the background of a statistically significant decrease in the blood level of 1,25(OH)2D3 combined with high levels of vitamin D-binding protein. This serves as a pathogenetic basis for the need to develop therapeutic and prophylactic schemes for prescribing vitamin D to children with urinary tract infections.

OR19-3 Differential Interactions of Vitamin D Binding Protein and Vitamin D Receptor in Different Ethnic Groups with Aggressive Thyroid Cancer

Abstract Thyroid cancer affects ethnic groups at different rates and severity. Despite this, thyroid cancer health disparities are still an understudied area. Our laboratory has shown a differential expression of vitamin D binding protein (DBP) in Filipino Americans (FA) versus European Americans (EA) [1]. Higher DBP levels correlate to a better prognosis. A study has revealed a DBP-dependent vitamin D receptor (VDR) promoter activation. In this study, we investigated whether VDR and DBP are expressed differentially in different ethnic groups, such as African Americans (AA), Hispanic Americans (HA), EA, and FA. We were also able to determine the differential DBP polymorphisms, VDR variant expressions, and DBP-VDR interactions within different ethnicities. By PCR-Restriction Fragment Length Polymorphism (PCR-RFLP), we determined a higher frequency of DBP gene polymorphism in FA versus EA. Analyzing the Cancer Genome Atlas (TCGA) thyroid cancer datasets with the UALCAN assay, we found the differential expressions of DBP and VDR genes based on cancer stages, sample types, race, and histological subtypes. By immunohistochemistry, we detected strong nuclear VDR (nVDR) and very low membranous VDR (mVDR) expression that correlated with low DBP in FA thyroid cancer tissues. In contrast, there was a higher expression of both mVDR and DBP in HA versus the other ethnicities. Co-immunoprecipitation analysis revealed a stronger DBP interaction with mVDR in FA compared to other ethnicities. Our data suggest that low DBP correlates with low mVDR in FA, whereas high DBP correlates with high mVDR in the other ethnicities. In conclusion, the strong interaction of DBP with mVDR in FA may implicate the potential role of DBP-mVDR crosstalk in aggressive thyroid cancer. Future research goals will be aimed at determining pathways involved in BDP-mVDR crosstalk in thyroid cancer health disparities. B. Mull, R. Davis, I. Munir, M.C. Perez, A.A. Simental, S. Khan, Differential expression of Vitamin D binding protein in thyroid cancer health disparities, Oncotarget 12(7) (2021) 596-607. Presentation: Monday, June 13, 2022 11:30 a.m. - 11:45 p.m.

Impaired Vitamin D Metabolism in Hospitalized COVID-19 Patients.

There is increasing data regarding the association between vitamin D and COVID-19. This study aimed to reveal the alterations of vitamin D metabolism in the setting of COVID-19. We examined 119 adult COVID-19 inpatients and 44 apparently healthy adult individuals with similar serum 25OH-D3 levels as a reference group. The assessment included serum biochemical parameters (total calcium, albumin, phosphorus, creatinine), parathyroid hormone (PTH), vitamin D-binding protein (DBP), vitamin D metabolites (25OH-D3, 25OH-D2, 1,25(OH)2D3, 3-epi-25OH-D3, 24,25(OH)2D3 and D3) and free 25OH-D. COVID-19 patients had in general very low vitamin D levels (median 25OH-D3 equals 10.8 ng/mL), accompanied by an increased production of the active vitamin D metabolite (1,25(OH)2D3), estimated as higher 1,25(OH)2D3 serum levels (61 [44; 81] vs. 40 [35; 50] pg/mL, p < 0.001) and lower 25OH-D3/1,25(OH)2D3 ratio (175 [112; 260] vs. 272 [200; 433], p < 0.001) which is presumably aimed at preventing hypocalcemia. Patients with COVID-19 also had elevated DBP (450 [386; 515] vs. 392 [311; 433] mg/L, p < 0.001) and low free 25OH-D levels (<LoB vs. 3.9 [3.2; 4.4] pg/mL, p < 0.001). Follow-up assessment of the COVID-19 inpatients showed recovery of the observed changes. Overall, hospitalized patients with an acute course of COVID-19 have not only very low levels of 25OH-D but also profound abnormalities in the metabolism of vitamin D regardless of the clinical course of the disease. These alterations might exacerbate existing vitamin D deficiency and its negative impact.

Free vitamin D3 index and vitamin D-binding protein in multiple sclerosis: A presymptomatic case-control study.

Background and purposeHigh levels of 25‐hydroxyvitamin D3 (25[OH]D3) are associated with a lower risk for multiple sclerosis (MS). The bioavailability of 25(OH)D3 is regulated by its main plasma carrier, vitamin D‐binding protein (DBP). Free 25(OH)D3 can be estimated by also measuring DBP concentration. In addition, DBP has immunomodulatory functions that may independently affect MS pathogenesis. No previous studies have assessed free 25(OH)D3 or DBP in presymptomatically collected samples. This study was undertaken to assess free 25(OH)D3 and DBP as risk factors for MS.MethodsA nested case–control study was performed with presymptomatic serum samples identified through cross‐linkage of MS registries and Swedish biobanks. Concentration of 25(OH)D3 was measured with liquid chromatography and DBP levels with sandwich immunoassay. Free 25(OH)D3 was approximated as free vitamin D3 index: (25[OH]D3/DBP) × 103. MS risk was analyzed by conditional logistic regression, calculating odds ratios (ORs) with 95% confidence intervals (CIs).ResultsSerum samples from 660 pairs of matched cases and controls were included.At <20 years of age, high levels of free vitamin D3 index were associated with a lower risk of MS (highest vs. lowest quintile: OR = 0.37, 95% CI = 0.15–0.91, p for trend across quintiles = 0.04). At age 30–39 years, high levels of DBP were associated with a lower MS risk (highest vs. lowest quintile: OR = 0.36, 95% CI = 0.15–0.85, p for trend = 0.02).ConclusionsThese findings support the hypothesis that high levels of free 25(OH)D3 at a young age reduce the risk of MS later in life. They also implicate a role for DBP in MS etiology.

Vitamin D, vitamin D—binding protein, free vitamin D and COVID-19 mortality in hospitalized patients

ABSTRACTBackgroundVitamin D deficiency has been associated with worse coronavirus disease 2019 (COVID-19) outcomes, but circulating 25-hydroxyvitamin D [25(OH)D] is largely bound to vitamin D–binding protein (DBP) or albumin, both of which tend to fall in illness, making the 25(OH)D status hard to interpret. Because of this, measurements of unbound (“free”) and albumin-bound (“bioavailable”) 25(OH)D have been proposed.ObjectivesWe aimed to examine the relationship between vitamin D status and mortality from COVID-19.MethodsIn this observational study conducted in Liverpool, UK, hospitalized COVID-19 patients with surplus sera available for 25(OH)D analysis were studied. Clinical data, including age, ethnicity, and comorbidities, were extracted from case notes. Serum 25(OH)D, DBP, and albumin concentrations were measured. Free and bioavailable 25(OH)D were calculated. Relationships between total, free, and bioavailable 25(OH)D and 28-day mortality were analyzed by logistic regression.ResultsThere were 472 patients with COVID-19 included, of whom 112 (23.7%) died within 28 days. Nonsurvivors were older (mean age, 73 years; range, 34–98 years) than survivors (mean age, 65 years; range, 19–95 years; P = 0.003) and were more likely to be male (67%; P = 0.02). The frequency of vitamin D deficiency [25(OH)D < 50 nmol/L] was similar between nonsurvivors (71/112; 63.4%) and survivors (204/360; 56.7%; P = 0.15) but, after adjustments for age, sex, and comorbidities, increased odds for mortality were present in those with severe deficiency [25(OH)D < 25 nmol/L: OR, 2.37; 95% CI, 1.17–4.78] or a high 25(OH)D (≥100 nmol/L; OR, 4.65; 95% CI, 1.51–14.34) compared with a 25(OH)D value of 50–74 nmol/L (reference). Serum DBP levels were not associated with mortality after adjustments for 25(OH)D, age, sex, and comorbidities. Neither free nor bioavailable 25(OH)D values were associated with mortality.ConclusionsVitamin D deficiency, as commonly defined by serum 25(OH)D levels (<50 nmol/L), is not associated with increased mortality from COVID-19, but extremely low (<25 nmol/L) and high (>100 nmol/L) levels may be associated with mortality risks. Neither free nor bioavailable 25(OH)D values are associated with mortality risk. The study protocol was approved by the London-Surrey Research Ethics Committee (20/HRA/2282).

Characterization of vitamin D metabolism in active acromegaly in the setting of bolus (150,000 IU) cholecalciferol treatment.

To reveal distinctive features of vitamin D metabolism in patients with active acromegaly compared to healthy individuals, particularly in the setting of cholecalciferol treatment. The study group included 34 adults with active acromegaly, and the control group included 30 apparently healthy adults with similar age, sex, and BMI. All participants received a single dose (150,000 IU) of cholecalciferol aqueous solution orally. Laboratory assessments including serum vitamin D metabolites (25(OH)D3, 25(OH)D2, 1,25(OH)2D3, 3-epi-25(OH)D3 and 24,25(OH)2D3), free 25(OH)D, vitamin D-binding protein (DBP) and parathyroid hormone (PTH) as well as serum and urine biochemical parameters were performed before the intake and on Days 1, 3, and 7 after the administration. All data were analyzed with nonparametric statistics. Patients with acromegaly had tendency to lower baseline 25(OH)D3 levels (p = 0.05) and lower 25(OH)D3 levels (p < 0.05) during the follow-up. They were also characterized by PTH suppression (lower baseline PTH levels and lower prevalence of secondary hyperparathyroidism), altered production of main vitamin D metabolites (higher 1,25(OH)2D3 and lower 24,25(OH)2D3 levels with corresponding lower 25(ОН)D3/1,25(ОН)2D3 and higher 25(ОН)D3/24,25(ОН)2D3 ratios) as well as concordant biochemical features (higher levels of serum phosphorus and albumin-adjusted calcium levels) throughout the study (p < 0.05). The acromegaly group showed an increase in DBP levels after cholecalciferol intake as opposed to the control group (p < 0.05) and had lower increase in free 25(OH)D levels (p < 0.05). Δ25(OH)D3 was similar between the groups (p > 0.05), showed a negative correlation with the disease activity markers-both IGF-1 levels (r = -0.44, p < 0.05) and fasting GH levels (r = -0.56, p < 0.05)-and lacked correlation with BMI in the acromegaly group (p > 0.05). Patients with active acromegaly have dysregulated vitamin D metabolism characterized by higher 1,25(ОН)2D3, lower 24,25(ОН)2D3 and altered DBP production. The response to vitamin D supplementation in acromegaly patients might be influenced by hormonal excess. Obtained results require reproducibility check and further study to develop specific clinical recommendations. NCT04844164 (release date: April 9, 2021; retrospectively registered).

Vitamin D-Binding Protein and the Free Hormone Hypothesis for Vitamin D in Bio-Naïve Patients with Psoriasis.

High levels of vitamin D-binding protein (DBP) have been reported in patients with psoriasis and the possibility of DBP as a marker of inflammation has been discussed. Furthermore, high DBP levels might negatively affect free 25(OH)D concentrations. According to the free hormone hypothesis, only the free fraction of a steroid hormone is capable of exerting biological action. Thus, free 25(OH)D level could be a better biomarker of vitamin D status than total 25(OH)D level. The objectives of this study were to identify the strongest determinants for DBP levels and to test the free hormone hypothesis for vitamin D in psoriasis. Additionally, we also aimed to investigate correlations between directly measured free 25(OH)D levels in serum and psoriasis disease severity compared to total 25(OH)D levels. This was a retrospective cross-sectional study including 40 bio-naïve patients with mild to severe plaque psoriasis. Psoriasis disease severity was evaluated using high sensitivity C-reactive protein (hsCRP), Psoriasis Area Severity Index (PASI) and visual analogue scale (VAS). Vitamin D metabolites including directly measured free 25(OH)D and serum DBP levels were measured. DBP levels were higher in patients with self-reported arthropathy than those without irrespective of confounding factors like sex, age and body weight. Total and free 25(OH)D levels correlated well (ρ = 0.77, p < 0.0001) and both were inversely correlated to intact parathyroid hormone (iPTH) (ρ = −0.33, p = 0.038 for total 25(OH)D and ρ = −0.40, p = 0.010 for free 25(OH)D). Only total 25(OH)D correlated to serum calcium levels (ρ = 0.32, p = 0.047). No correlations between any of the vitamin D metabolites and psoriasis disease severity were observed. In conclusion, DBP might be a new inflammatory biomarker in psoriasis, especially in psoriatic arthritis. Total 25(OH)D was a reliable measure for vitamin D status in this psoriasis cohort. However, evaluation of free 25(OH)D in patients with psoriatic disease and multiple co-morbidities and/or ongoing biologic treatment should be considered.

Evaluation of serum and gingival crevicular fluid levels of Vitamin D binding protein in subjects with clinically healthy periodontium and chronic periodontitis: A clinico bio-chemical study.

Advances in oral and periodontal disease diagnostic research are moving towards methods wherein periodontal risk can be identified and quantified by objective measures such as bio-markers. Given the roles of vitamin D binding protein (DBP) in modulating the immune response and in the transport of vitamin D, it is hypothesised that quantitative changes of vitamin DBP are associated with periodontal disease. The aim of the current study is to measure DBP levels in serum and gingival crevicular fluid (GCF) of patients with generalised chronic periodontitis, in comparison to healthy controls. The present cross-sectional clinico-bio-chemical study includes 30 systemically healthy subjects with 15 periodontally healthy and 15 chronic periodontitis subjects who were recruited from the out-patient Department of Periodontics. GCF and blood samples were collected from all the patients. DBP estimation was performed in both the samples using a commercially available ELISA kit. Serum and GCF DBP levels in chronic periodontitis subjects were significantly higher when compared to the periodontally healthy group. There were no significant correlations found among serum and GCF DBP levels with gender and increasing age in both the groups. An increase in disease severity measured by the increase in probing pocket depth and clinical attachment loss did not show correlation with the GCF and serum DBP levels in the chronic periodontitis group. Based on the findings of the present study, increased serum and GCF DBP levels in chronic periodontitis seem to be a probable marker for identifying ongoing periodontal destruction.

Vitamin D status and serum vitamin D binding protein levels in Nigerian children with nephrotic syndrome

Introduction: Nephrotic syndrome is a chronic relapsing condition associated with urinary loss of albumin and other proteins such as vitamin D binding protein (DBP). We determined vitamin D status and serum DBP levels in children with nephrotic syndrome and compared them to healthy controls. Methods: A cross-sectional study was performed over a six-month period in children less than 18 years of age. The children with nephrotic syndrome were categorised by disease status as either newly diagnosed, in remission, resistant to therapy, or in relapse. Vitamin D levels were regarded as sufficient if ≥75 nmol/L, insufficient if &lt;75 nmol/L but ≥50 nmol/L, deficient if &lt;50 nmol/L, and severely deficient if &lt;25 nmol/L. Serum DBP was also measured. Results: Fifty-five children with nephrotic syndrome and 24 controls were included in the study. There was no significant difference between the median ages of the cases (72.0 months, interquartile range (IQR) 48.0–120.0 months) and the controls (84.0 months, IQR 39.0–129.0 months). Severe vitamin D deficiency, deficiency and insufficient levels were documented in 54.5%, 41.8% and 3.6% of cases, respectively, significantly lower than the controls (P = 0.003). Vitamin D levels were higher in children with nephrotic syndrome in remission than in those who were not (30.3 ± 15.2 nmol/L vs 19.6 ± 11.0 nmol/L, P = 0.004). In the groups who were in remission, newly diagnosed, relapsing, and resistant, the median vitamin D levels were 30.3 nmol/L, 20.1 nmol/L, 19.2 nmol/L and 9.4 nmol/L, respectively (P = 0.031). Conclusions: Hypovitaminosis D occurs frequently in Nigerian children with nephrotic syndrome as well as in apparently healthy controls. Routine supplementation of vitamin D should be considered in children with nephrotic syndrome irrespective of whether the disease is in remission or not, or whether it is steroid-sensitive or not. Keywords: nephrotic syndrome, vitamin D deficiency, vitamin D binding protein

Assessment of Vitamin D Metabolism in Patients with Cushing’s Disease in Response to 150,000 IU Cholecalciferol Treatment

In this study we aimed to assess vitamin D metabolism in patients with Cushing’s disease (CD) compared to healthy individuals in the setting of bolus cholecalciferol treatment. The study group included 30 adults with active CD and the control group included 30 apparently healthy adults with similar age, sex and BMI. All participants received a single dose (150,000 IU) of cholecalciferol aqueous solution orally. Laboratory assessments including serum vitamin D metabolites (25(OH)D3, 25(OH)D2, 1,25(OH)2D3, 3-epi-25(OH)D3 and 24,25(OH)2D3), free 25(OH)D, vitamin D-binding protein (DBP) and parathyroid hormone (PTH) as well as serum and urine biochemical parameters were performed before the intake and on Days 1, 3 and 7 after the administration. All data were analyzed with non-parametric statistics. Patients with CD had similar to healthy controls 25(OH)D3 levels (p > 0.05) and higher 25(OH)D3/24,25(OH)2D3 ratios (p < 0.05) throughout the study. They also had lower baseline free 25(OH)D levels (p < 0.05) despite similar DBP levels (p > 0.05) and lower albumin levels (p < 0.05); 24-h urinary free cortisol showed significant correlation with baseline 25(OH)D3/24,25(OH)2D3 ratio (r = 0.36, p < 0.05). The increase in 25(OH)D3 after cholecalciferol intake was similar in obese and non-obese states and lacked correlation with BMI (p > 0.05) among patients with CD, as opposed to the control group. Overall, patients with CD have a consistently higher 25(OH)D3/24,25(OH)2D3 ratio, which is indicative of a decrease in 24-hydroxylase activity. This altered activity of the principal vitamin D catabolism might influence the effectiveness of cholecalciferol treatment. The observed difference in baseline free 25(OH)D levels is not entirely clear and requires further study.

Total and free vitamin D metabolites in patients with primary hyperparathyroidism.

To evaluate total and free vitamin D metabolites and hormone-to-prohormone [1,25(OH)2D/25(OH)D] "activation ratio" in PHPT patients with low or insufficient vitamin D status. Thirty female patients with primary hyperparathyroidism (PHPT) and 30 age and body mass index (BMI) matched healthy controls were enrolled. Serum levels of calcium, intact parathyroid hormone (iPTH), vitamin D binding protein (DBP), albumin, total 25(OH)D and 1,25(OH)2D were measured. The activation ratio of vitamin D was calculated as total 1,25(OH)2D/25(OH)D. Calculated serum-free 25(OH)D and 1,25(OH)2D levels were also reported. Compared to the control subject, patients with PHPT had a lower total 25(OH)D and DBP levels (p < 0.001). The serum concentration of free 25(OH)D and total 1,25(OH)2D were similar between the two groups; but free 1,25(OH)2D levels were about 26% higher in the PHPT patients compared to controls (p < 0.001). PHPT patients had a significantly higher activation ratio (p < 0.01), although their total 25(OH)D were lower than controls. The free (but not total) 1,25(OH)2D level was inversely correlated with DBP (p < 0.01). Both free 1,25(OH)2D levels and activation ratio were positively correlated with iPTH and calcium levels (p < 0.01). The activation ratio was highly correlated with levels of total vitamin D stores and free vitamin D metabolites (p < 0.001). Patients with PHPT had significantly higher free 1,25(OH)2D levels and activation ratio compared to control subjects. We suggest that levels of free vitamin D metabolites and vitamin D activation ratio may provide additional values for the diagnosis and therapeutic choices in these patient populations with compromised vitamin D status.

Association of blood lead level with vitamin D binding protein, total and free 25-hydroxyvitamin D levels in middle-school children.

A negative association between blood Pb level (BPbL) and vitamin D metabolites in occupationally exposed populations has been reported, but data from the general population are scarce. Furthermore, the association between BPbL and vitamin D binding protein (DBP) and free 25-hydroxyvitamin D (25(OH)D) has not been reported. We investigated the association of BPbL with DBP, total and free 25(OH)D in healthy adolescents (n 1347; age range 11-16 years) cross-sectionally selected from all Governorates of Kuwait, utilising multi-stage cluster random sampling. Pb in whole blood was analysed by inductively coupled plasma MS, and DBP with ELISA. Plasma 25(OH)D was analysed by LC-MS/MS, and free 25(OH)D was calculated utilising the levels and binding affinities of DBP and albumin for 25(OH)D. DBP was positively associated with BPbL (β = 0·81; 95 % CI 0·14, 0·22; P < 0·001). A negative association between BPbL and total 25(OH)D was non-significant (P = 0·24) when BPbL was used as a continuous variable but was significant when used as quartiles (P = 0·02). The negative association between BPbL and free 25(OH)D was significant whether BPbL was used as continuous, as quartiles or as cut-off point of <5 µg/dl (0·24 µmol/l). In multinomiallogistic regression, the odds of vitamin D insufficiency and deficiency were more than two-fold higher in the upper quartiles of BPbL compared with the lowest quartile. The negative correlation of BPbL with free 25(OH)D was more robust than its correlation with total 25(OH)D. Future studies must consider the levels of DBP when assessing the association between Pb and vitamin D metabolites.

High levels of serum vitamin D-binding protein in patients with psoriasis: A case-control study and effects of ultraviolet B phototherapy

The role of vitamin D in psoriasis remains contradictory despite the fact that vitamin D analogues constitute an established treatment for psoriasis. It has been proposed that the ability of vitamin D to exert anti-inflammatory effects might not depend solely on the concentration of serum 25(OH)D but also on the concentration of vitamin D-binding protein (DBP). High concentrations of DBP might diminish vitamin D’s biologic action. The aims of this study were (i) to analyze the serum levels of DBP, total and calculated free 25(OH)D in patients with psoriasis and compare the results with healthy controls and (ii) to study the effect of ultraviolet B (UVB) phototherapy on DBP levels. Caucasian subjects (n = 68) with active plaque psoriasis were compared with a population-based sample of men and women (n = 105), matched for age and sex. Season of enrollment was taken into consideration. The patients were also studied before and after UVB phototherapy. The severity of the disease was calculated as Psoriasis Area Severity Index (PASI). DBP, free 25(OH)D index and total 25(OH)D were higher in patients with psoriasis compared with controls (P= 0.004, P = 0.045 and P < 0.0001, respectively). DBP did not change after phototherapy, whereas 25(OH)D increased and intact parathyroid hormone (iPTH) decreased (P < 0.001 for both). Psoriasis improved and PASI decreased after phototherapy (P < 0.001). There was no correlation between DBP and 25(OH)D or between DBP and PASI. Measurement of DBP is recommended when evaluating vitamin D status in patients with psoriasis. High DBP levels in psoriasis imply a disturbed vitamin D pathway that warrants further investigation. Direct measurement of free 25(OH)D, instead of total 25(OH)D that circumvents abnormally high levels of DBP, could be considered.

Impact of Vitamin D Elements in Insulin Sensitivity in Type 2 Diabetes Mellitus (DM2)

Numerous non-skeletal diseases have been reported to be associated with vitamin D status including type2diabetes mellitus (T2DM). Different studies provide evidence that vitamin D status as well as other elementssuch as vitamin D binding protein (DBP) and vitamin D receptor (VDR) may play substantial role in glucosetolerance. Present study was designed to investigate the role of vitamin D status and their elements ininsulin resistance or sensitivity in T2DM patients Current study includes 84 participants of both gender(56 patients and 28 as control). Clinical samples were collected from clinically proved DM2 patients.Serum levels of insulin, FBS, VD, VDR, and DBP were measured of each subjects. Using of HomeostasisModel Assessment Insulin resistance (HOMA-IR), T2DM patients were sub grouped to insulin resistance(IR) and insulin sensitivity (IS) groups. Relations among studied factors, FBS showed significant positiveand negative relation with HOMA-IR and VD3 respectively, furthermore HOMA-IR revealed significantpositive relation with DBP and VDR. Also, DBP revealed significant positive relation with each of VDRand HOMA-IR. On the other hand, VD3 levels showed significant and non-significant elevation in IS groupcompared to C and IR group respectively, while DBP revealed significant and non-significant dropping in ISgroup compared to C and IR groups respectively. Levels of VDR in IS group showed significant droppingcompared to C and IR groups respectively. Our study concludes that VD3 alone or with its elements playsubstantial role in regulation of blood sugar levels particularly related to insulin sensitivity