D-binding Protein Concentrations Research Articles

The association between vitamin D binding protein levels and periodontal status: A systematic review.

Vitamin D binding protein (DBP) is biosynthesised in the liver and is predominantly expressed in serum. Its primary role centres on facilitating the systemic transportation of vitamin D and its metabolites, notably 25-hydroxyvitamin D, to specific target tissues where vitamin D exerts its biological functions. Due to the paucity of studies, it is unclear whether there is an association between DBP and periodontal status and thus its potential use as a diagnostic biomarker. Therefore, the aim of the systematic review is to investigate the association between DBP in periodontal disease. Two independent reviewers (YD and RG) performed a systematic literature search of English publications using several databases including MEDLINE (OVID interface, 1946 onwards), EMBASE (OVID interface, 1974 onwards), and Global Health (OVID interface, 1973 onwards). This search strategy enabled the identification of relevant publications and the development of a comprehensive library of studies. Studies were included based on previously agreed eligibility criteria. Of the eight studies included as part of this systematic review, seven were case-control studies and one was a cross-sectional study. The quality assessment was based on the Newcastle-Ottawa Scale (NOS) for case-control studies and the modified NOS for the cross-sectional study. The NOS quality assessment was 'favorable' for 6 included case control studies; and 'fair' for one study. The modified NOS quality assessment for the single cross-sectional study demonstrated a medium risk of bias. The results of the majority of the included studies indicated a statistically significant higher concentration of DBP levels in individuals with periodontitis in comparison to those who were periodontally healthy. This trend held true irrespective of the sampling method employed for the assessment of DBP concentration. The results summarised in this systematic review indicate a positive association between DBP and periodontitis. Nonetheless, there is a need for longitudinal, prospective trials, to confirm the use of DBP as a potential biomarker for the diagnosis of periodontitis.

Vitamin D Binding Protein and Postsurgical Outcomes and Tissue Injury Markers After Hip Fracture: A Prospective Study.

Hip fracture is a serious injury that can lead to increased morbidity and mortality. Vitamin D binding protein (DBP) is a potential prognostic indicator of outcomes since it is important for actin scavenging and inflammation after tissue injury. To determine whether circulating DBP is associated with mobility or mortality after hip fracture and its association with acute tissue injury markers. Post hoc analysis of a multisite North American prospective study of 260 patients with hip fracture; mobility assessed at 30 and 60 days and mortality at 60 days after repair surgery. Biochemical markers were measured before, and 2 to 4 days after surgery. Tissue injury markers were measured in 100 randomly selected patients and controls. The primary outcome was mobility and mortality by DBP tertiles. Secondary outcomes were assessment of pre- and postoperative biomarkers. Among all patients (81 ± 9 years, BMI 25 ± 4 kg/m2; 72% female), the highest DBP tertile had greater mobility at 30 (OR: 2.66; 95% CI: 1.43, 4.92; P = .002) and 60 days (OR: 2.31; 95% CI: 1.17, 4.54; P = .014) and reduced mortality (OR: 0.18; 95% CI: 0.04, 0.86; P = .032) compared with the lowest DBP tertile (<28.0 mg/dL). Total 25-hydroxyvitamin-D did not differ between tertiles (22.0 ± 9.5 ng/mL). Circulating DBP and gelsolin were lower and interleukin-6, C-reactive protein, and F-actin were higher (P < .01) in patients vs controls, and worsened (P < .01) after surgery. High circulating DBP concentrations are associated with better mobility and reduced mortality after hip fracture surgery. The role of DBP as an acute phase reactant to tissue injury and clinical outcomes should be addressed in future study.

Serum 25-hydroxyvitamin D, vitamin D receptor, and vitamin D binding protein concentrations in dogs with acute pancreatitis compared to healthy control dogs.

Previous studies have documented vitamin D imbalance in dogs with acute pancreatitis (AP), but no studies have investigated serum vitamin D receptor (VDR) and vitamin D-binding protein (VDBP) concentrations. Compare serum 25-hydroxyvitamin D (25[OH]D), VDR, and VDBP concentrations in healthy dogs and dogs with AP and identify correlations between these concentrations with ionized calcium, C-reactive protein (CRP), and canine-specific pancreatic lipase (Spec cPL) concentrations. Twenty-two dogs with AP and 20 healthy control dogs. Prospective cross-sectional study. Serum 25(OH)D concentrations were measured using a chemiluminescence immunoassay, and VDR and VDBP concentrations were measured using a ELISA kit designed for dogs. Serum concentrations of 25(OH)D were lower in dogs with AP (mean ± SD, 66.1 ± 39.2 ng/mL) than in controls (96.8 ± 30.4 ng/mL; P = .01), and VDR concentrations were lower in dogs with AP (5.3 ± 3.5 ng/mL) than in controls (7.4 ± 2.5 ng/mL; P = .03). No difference was observed in serum VDBP concentrations between the groups. Serum VDR concentrations differed between survivors (median [interquartile range] = 6.6 [4.3-8.2] ng/mL) and nonsurvivors (2.7 [0.5-3.5] ng/mL; P = .01). Negative correlations were observed among serum VDR, CRP (rs = -0.55), and Spec cPL (rs = -0.47) concentrations in dogs with AP. Dogs with AP had lower serum 25(OH)D and VDR concentrations than controls. Additionally, our study suggests a potential role of VDR expression in the inflammatory process of AP in dogs.

Changes in Skeletal Muscle Troponin T and Vitamin D Binding Protein (DBP) Concentrations in the Blood of Male Amateur Athletes Participating in a Marathon and 100 km Adventure Race

This study assessed changes in creatine kinase (CK) activity and skeletal muscle troponin T (sTnT) concentrations in the blood, to estimate the degree of muscle degradation after exercise. In addition, the concentration of vitamin D binding protein (DBP) in the blood was assessed. DBP concentrations were measured in blood as a marker for plasma load by monomeric actin. The study included marathon (MR) participants and 100 km adventure race (AR) participants, who were examined before and after the race. There was a significant (16-fold) increase in CK activity among AR participants, and a significant increase in sTnT concentration-127% in the MR group and 113% in the AR group, while there was a statistically significant decrease in DBP concentration by 14% in the AR group. In addition, it was observed that the initial concentration of DBP in both groups was in a normal range, but was lower than the average population, and the DBP concentration in the AR group was lower than in the MR group. It was concluded that exhausting physical effort such as a marathon or adventure races causes muscle damage with a far stronger influence on sarcoplasm than on filaments. The short-term and slight reduction in the concentration of DBP in blood after such efforts may be due to the appearance of monomeric actin in plasma.

Genetic correlates of vitamin D-binding protein and 25-hydroxyvitamin D in neonatal dried blood spots

The vitamin D binding protein (DBP), encoded by the group-specific component (GC) gene, is a component of the vitamin D system. In a genome-wide association study of DBP concentration in 65,589 neonates we identify 26 independent loci, 17 of which are in or close to the GC gene, with fine-mapping identifying 2 missense variants on chromosomes 12 and 17 (within SH2B3 and GSDMA, respectively). When adjusted for GC haplotypes, we find 15 independent loci distributed over 10 chromosomes. Mendelian randomization analyses identify a unidirectional effect of higher DBP concentration and (a) higher 25-hydroxyvitamin D concentration, and (b) a reduced risk of multiple sclerosis and rheumatoid arthritis. A phenome-wide association study confirms that higher DBP concentration is associated with a reduced risk of vitamin D deficiency. Our findings provide valuable insights into the influence of DBP on vitamin D status and a range of health outcomes.

Increased Serum Total and Free 25-Hydroxyvitamin D with Daily Intake of Cholecalciferol-Fortified Skim Milk: A Randomized Controlled Trial in Colombian Adolescents

BackgroundThe efficacy of cholecalciferol (vitamin D3) food fortification in low- and middle-income countries near the Equator is unknown. ObjectivesWe examined the effects of providing cholecalciferol-fortified skim milk to adolescents and their mothers on serum total 25(OH)D, free 25(OH)D, and vitamin D–binding protein (DBP) concentrations in a randomized controlled trial. MethodsWe randomly assigned 80 Colombian families each with a child aged 12–14.5 y and their mother 1 L of skim milk daily, either fortified with 2400 IU (60 μg) cholecalciferol or unfortified, for 6 wk. We prescribed 500 mL of milk daily to adolescents; mothers consumed the remainder ad libitum. We estimated intent-to-treat effects as the between-arm difference in the change in serum total and free 25(OH)D and DBP concentrations from baseline to the end of follow-up. Secondary analyses included stratification by baseline characteristics and per-protocol comparisons. ResultsAmong adolescents, fortification effects (95% CI) on serum total 25(OH)D, free 25(OH)D, and DBP concentrations were 5.4 nmol/L (2.1, 8.8 nmol/L), 0.6 pmol/L (−0.2, 1.4 pmol/L), and −416 nmol/L (−944, 112 nmol/L), respectively. Effects on total 25(OH)D were stronger in adolescents with lower DBP concentrations, darker skin, less sunlight exposure, and higher compliance than in their respective counterparts. Fortification increased free 25(OH)D concentrations in high compliers. Among mothers, the effects (95% CI) on total 25(OH)D and DBP concentrations were 4.0 nmol/L (0.6, 7.5 nmol/L) and −128 nmol/L (−637, 381 nmol/L), respectively. There were no adverse events. ConclusionsProvision of cholecalciferol-fortified skim milk increases serum total 25(OH)D concentrations in Colombian adolescents and adult women.

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.

GC gene polymorphisms found with type 2 diabetes and low vitamin D status among rural Chinese in Henan province.

Accumulating evidence suggests that vitamin D may be involved in the pathogenesis of type 2 diabetes (T2D). Group-specific component (GC) gene is the most important transporter of vitamin D and plays a regulatory role in vitamin D metabolism. We aimed to evaluate the association of GC gene polymorphisms with T2D susceptibility and vitamin D status in the Chinese rural population. A total of 1372 subjects were eligible in this cross-sectional study. Three SNPs of the GC gene (rs7041, rs4588, and rs2282679) were genotyped by TaqMan probe assays. Logistic regression and Kruskal-Wallis one-way analysis were performed to determine the possible risk genotype for T2D and vitamin D metabolite concentrations, respectively. The serum 25-hydroxyvitamin D3 [25(OH)D3] and vitamin D binding protein (DBP) concentrations were significantly lower in the T2D group than the non-T2D group. GG genotype carriers of rs7041 (T>G) were more likely to have T2D compared with AA carriers (OR=2.00, 95% CI: 1.19-3.37). Variants of rs4588 (C>A) and rs2282679 (A>C) were associated with a lower risk of T2D under the dominant inheritance model (OR=0.65, 95% CI: 0.48-0.88; OR=0.66, 95% CI: 0.49-0.90, respectively). We further found that non-T2D subjects with the AA genotype of rs4588 had significantly higher 25(OH)D3 concentrations than the CC genotype (p=0.022). In contrast, the T2D cases with the CC genotype of rs2282679 had lower DBP concentrations compared to the AA genotype (p=0.020). Our study indicates a potential role for GC gene polymorphisms in T2D susceptibility and vitamin D metabolite concentrations in the Chinese rural population.

Vitamin D kinetics in nonpregnant and pregnant women after a single oral dose of trideuterated vitamin D3

The plasma pool of the hormone 1,25-dihydroxyvitamin D (1,25(OH)2D) is increased throughout most of human pregnancy. Mechanisms behind this adaptation are unclear, in part due to limited data on vitamin D kinetics during pregnancy. Stable isotopes make it possible to study vitamin D kinetics in vulnerable study populations like pregnant women. We conducted a pilot study of vitamin D kinetics in nonpregnant and pregnant women. We evaluated a clinical protocol and developed analytical methods to assess the serum appearance and disappearance of trideuterated vitamin D3 (d3-vitamin D3) and trideuterated 25-hydroxyvitamin D3 (d3-25(OH)D3) after a single oral dose of 25 μg of [6,19,19-2H]-vitamin D3 (d3-vitamin D3). Blood was collected at baseline and 2, 4, 6, 24, 168, 264, and 456 hours post-dosing. We then described the serum kinetic profiles of d3-vitamin D3 and d3-25(OH)D3 in nonpregnant and pregnant women. Serum kinetic profiles of d3-vitamin D3 and d3-25(OH)D3 followed a time course in line with previous pharmacokinetic studies. There was marked variability between participants in the area under the concentration-time curve (AUC) of d3-25(OH)D3 over the 20-day study period. This AUC of d3-25(OH)D3 was positively correlated with the serum vitamin D binding protein (DBP) concentration, which was higher in pregnant compared with nonpregnant women. The mean serum half-life of 25(OH)D3 was longer but not significantly different in pregnant women (18.8 days) compared with nonpregnant women (13.6 days). Our pilot study demonstrated that a single oral dose of 25 μg of d3-vitamin D3 can be used to study vitamin D kinetics. Serum DBP concentration is an important predictor of vitamin D kinetics, and more research is needed to fully understand the significance of elevated DBP concentration during pregnancy.

Macrophages Control the Bioavailability of Vitamin D and Vitamin D-Regulated T Cell Responses.

The active form of vitamin D3 (1,25(OH)2D3) has a great impact on T cell effector function. Thus, 1,25(OH)2D3 promotes T helper 2 (Th2) and regulatory T (Treg) cell function and concomitantly inhibits Th1 and Th17 cell function. Thus, it is believed that vitamin D exerts anti-inflammatory effects. However, vitamin D binding protein (DBP) strongly binds both 1,25(OH)2D3 and the precursor 25(OH)D3, leaving only a minor fraction of vitamin D in the free, bioavailable form. Accordingly, DBP in physiological concentrations would be expected to block the effect of vitamin D on T cells and dendritic cells. In the present study, we show that pro-inflammatory, monocyte-derived M1 macrophages express very high levels of the 25(OH)D-1α-hydroxylase CYP27B1 that enables them to convert 25(OH)D3 into 1,25(OH)2D3 even in the presence of physiological concentrations of DBP. Co-cultivation of M1 macrophages with T cells allows them to overcome the sequestering of 25(OH)D3 by DBP and to produce sufficient levels of 1,25(OH)2D3 to affect T cell effector function. This study suggests that in highly inflammatory conditions, M1 macrophages can produce sufficient levels of 1,25(OH)2D3 to modify T cell responses and thereby reduce T cell-mediated inflammation via a vitamin D-mediated negative feed-back loop.

Elevated Plasma Concentrations of Vitamin D-Binding Protein Are Associated with Lower High-Density Lipoprotein and Higher Fat Mass Index in Overweight and Obese Women.

(1) Background: Observational studies have established that vitamin D-binding protein (DBP) and 25-hydroxyvitamin D3 (25(OH)D) concentrations are the major factors affecting the bioavailability of 25(OH)D. It has also been shown that poor 25(OH)D bioavailability elevates the risk of obesity and its related cardio-metabolic disorders. However, the relationship between 25(OH)D and DBP concentrations with cardio-metabolic risk factors in overweight and obese cohorts has not been established. Consequently, we evaluated the association between DBP and 25(OH)D concentrations with lipid profile, blood pressure (BP), and body composition in overweight and obese women. (2) Methods: In this cross-sectional study of 236 overweight and obese women, DBP and 25(OH)D concentrations were measured using an enzyme-linked immunosorbent assay. Body composition was assessed via bioelectrical impedance analysis. Lipid profile and BP were assessed by an auto-analyzer and digital BP monitor, respectively. The associations were examined by multivariate logistic regression. (3) Results: The indicated showed an inverse relationship between DBP and high-density lipoprotein (HDL) (p = 0.010) concentrations (where individuals with higher DBP had lower HDL) which, after adjusting for possible cofounders, remained significant (p = 0.006). Moreover, DBP concentration was positively associated with fat mass index (FMI) after adjustment (p = 0.022). No significant relationships were observed among 25(OH)D and target variables. (4) Conclusions: In conclusion, lower concentrations of HDL and higher values of FMI are associated with higher concentrations of DBP in overweight and obese women. These findings present novel awareness regarding the association of DBP with some metabolic and body composition variables in overweight and obese women. However, a two-way causal relationship between DBP and target variables should be considered.

Development and analytical validation of a novel bioavailable 25-hydroxyvitamin D assay.

BackgroundBioavailable 25-hydroxyvitamin D (25OHD) may be a better indicator of vitamin D sufficiency than total 25OHD. This report describes a novel assay for measuring serum bioavailable 25OHD.MethodsWe developed an assay for 25OHD % bioavailability based on competitive binding of 25OHD tracer between vitamin D-binding protein (DBP)-coated affinity chromatography beads and serum DBP. Bioavailable 25OHD, total 25OHD, albumin, and DBP protein concentrations were measured in 89 samples from hospitalized patients and 42 healthy controls to determine how the DBP binding assay responds to differences in concentrations of DBP and compares to calculated bioavailable 25OHD values.ResultsDBP binding assay showed a linear relationship between DBP-bound 25OHD tracer recovered from bead supernatant and DBP calibrator concentrations (y = 0.0017x +0.731, R2 = 0.9961, p<0.001). Inversion of this relationship allowed interpolation of DBP binding equivalents based upon 25OHD tracer recovered. The relationship between DBP binding equivalents and % bioavailability fits a non-linear curve, allowing calculation of % bioavailable 25OHD from DBP binding equivalents (y = 10.625x-0.817, R2 = 0.9961, p<0.001). In hospitalized patient samples, there were linear relationships between DBP protein concentrations and DBP binding equivalents (y = 0.7905x + 59.82, R2 = 0.8597, p<0.001), between measured vs. calculated % bioavailability (y = 0.9528 + 0.0357, R2 = 0.7200, p<0.001), and between absolute concentrations of measured vs. calculated bioavailable 25OHD (y = 1.2403 + 0.1221, R2 = 0.8913, p<0.001).ConclusionsThe DBP-binding assay for bioavailable 25OHD shows expected changes in 25OHD % bioavailability in response to changes in DBP concentrations and concordance with calculated bioavailable 25OHD concentrations.

Vitamin D-binding protein: multifunctional component of blood serum

Vitamin D-binding protein (DBP) was discovered more than half a century ago as a polymorphic serum protein and is currently characterized by a variety of physiological properties. First of all, DBP carries the bulk of vitamin D metabolites circulating in the bloodstream, while albumin is the second most important transport protein, especially in patients with a low concentration of DBP in serum. Since it was discovered that only 12% of the total circulating DBP have occupied steroid binding sites, a vigorous study of other potential biological roles of DBP was initiated: actin utilization, regulation of inflammation and innate immunity mechanisms, fatty acid binding, effects on bone metabolism and participation in the tumor pathogenesis. This review focuses on the main known biological functions of DBP.

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.

Preliminary validation of serotransferrin and vitamin D binding protein in the gingival crevicular fluid as candidate biomarkers for pubertal growth peak in subjects with Class I and Class II malocclusion

Identification of pubertal growth peak is of great importance for the orthopedic treatment of Class II malocclusion. Our previous work demonstrated that vitamin D binding protein (DBP) and serotransferrin (TF) in gingival crevicular fluid (GCF) could be candidate biomarkers of pubertal growth peak. This research aimed to preliminarily validate TF and DBP in subjects with Class I and Class II malocclusion, to compare their diagnostic accuracy, and to construct a statistic model to help the diagnosis of skeletal pubertal peak. Sixty-six circumpubertal subjects were recruited, including 32 subjects with Class I malocclusion and 34 subjects with Class II malocclusion. All subjects were divided into prepubertal, pubertal, and postpubertal groups according to their cervical vertebral maturation stages. GCF samples were collected, and the concentration of DBP and TF were detected by enzyme-linked immunosorbent assay. Percentage of TF in GCF was significantly higher in pubertal than in prepubertal and postpubertal groups, in subjects with Class I and Class II malocclusion, whereas the difference observed in DBP was less significant. The diagnostic accuracy of TF was better than DBP and chronological age. The most optimal thresholds of maxillary and mandibular TF in distinguishing pubertal from nonpubertal subjects were 4.20% and 4.09%, respectively. The combination of TF and age exhibited the best diagnostic accuracy. TF in GCF could be considered as a potential biomarker of pubertal peak and can assist the diagnosis of skeletal pubertal peak.

Trophoblast uptake of DBP regulates intracellular actin and promotes matrix invasion.

Early pregnancy is characterised by elevated circulating levels of vitamin D binding protein (DBP). The impact of this on maternal and fetal health is unclear but DBP is present in the placenta, and DBP gene variants have been linked to malplacentation disorders such as preeclampsia. The functional role of DBP in the placenta was investigated using trophoblastic JEG3, BeWo and HTR8 cells. All three cell lines showed intracellular DBP with increased expression and nuclear localisation of DBP in cells treated with the active form of vitamin D, 1,25-dihydroxyvitamin D (1,25D). When cultured in the serum of mice lacking DBP (DBP-/-), JEG3 cells showed no intracellular DBP indicating uptake of exogenous DBP. Inhibition of the membrane receptor for DBP, megalin, also suppressed intracellular DBP. Elimination of intracellular DBP with DBP-/- serum or megalin inhibitor suppressed matrix invasion by trophoblast cells and was associated with increased nuclear accumulation of G-actin. Conversely, treatment with 1,25D enhanced matrix invasion. This was independent of the nuclear vitamin D receptor but was associated with enhanced ERK phosphorylation, and inhibition of ERK kinase suppressed trophoblast matrix invasion. When cultured with serum from pregnant women, trophoblast matrix invasion correlated with DBP concentration, and DBP was lower in first-trimester serum from women who later developed preeclampsia. These data show that the trophoblast matrix invasion involves uptake of serum DBP and associated intracellular actin-binding and homeostasis. DBP is a potential marker of placentation disorders such as preeclampsia and may also provide a therapeutic option for improved placenta and pregnancy health.

Free and Bioavailable Fractions of Vitamin D: Association with Maternal Characteristics in Brazilian Pregnant Women.

Normal pregnancy is characterized by many changes in vitamin D metabolism, challenging the assessment of vitamin D status based exclusively on serum total 25-hydroxyvitamin D (25(OH)D). We hypothesized that measuring free and bioavailable fractions contributes to a better vitamin D status assessment in late pregnancy. Our aim was to evaluate a broad set of biomarkers of vitamin D status in Brazilian women in the third trimester of pregnancy. This cross-sectional study was conducted in women (n = 123, 18–44 y, 27–41 wk gestation) attended in a public maternity in Rio de Janeiro (2016–2018). Biomarkers included serum concentrations of total 25(OH)D3, parathyroid hormone (PTH), vitamin D-binding protein (DBP), and free and bioavailable fractions of 25(OH)D3. Vitamin D insufficiency (<50 nmol/L) was prevalent in 47.9% of the pregnant women. Serum 25(OH)D3 was inversely associated with the gestational week (β = −0.71, 95% confidence interval (CI): −1.31 to −0.16) and season, being lower in autumn (β = −9.90, 95% CI: −16.14 to -3.64) and winter (β = −16.74, 95%CI: −23.13 to −10.34). Concentrations of DBP, and free and bioavailable 25(OH)D3 were also inversely associated with winter months (P < 0.05). DBP was directly associated with prepregnancy BMI (β = 5.84, 95% CI: 0.62 to 11.06). The recognized season-effect on total 25(OH)D3 appeared to also occur on free and bioavailable fractions. Although advanced gestational age was associated with lower total 25(OH)D3, our results suggest an adaptive mechanism responsible for maintaining free fraction during the 3rd trimester. We also suggest that starting pregnancy in obese condition may have an impact on vitamin D bioavailability, which deserves further investigation.

Vitamin D Deficiency in Middle Childhood Is Related to Behavior Problems in Adolescence

Background:Vitamin D deficiency (VDD) is associated with depression and schizophrenia in adults. The effect of VDD in childhood on behavioral development is unknown. Objectives:We aimed to study the associations of VDD and vitamin D binding protein (DBP) in middle childhood with behavior problems in adolescence. Methods:We quantified plasma total 25-hydroxyvitamin D [25(OH)D] and DBP in 273 schoolchildren aged 5–12 y at recruitment into a cohort study in Bogota, Colombia. Externalizing and internalizing behavior problems were assessed after a median 6-y follow-up by parental report [Child Behavior Checklist (CBCL)] and self-report [Youth Self-Report (YSR)]. We estimated mean problem score differences with 95% CIs between exposure categories using multivariable linear regression. We also compared the prevalence of clinical behavior problems (score >63) between exposure groups. We assessed whether the associations between DBP and behavior problems were mediated through VDD. Results:Mean ± SD CBCL and YSR externalizing problems scores were 56.5 ± 9.3 and 53.2 ± 9.5, respectively. Internalizing problems scores averaged 57.1 ± 9.8 and 53.7 ± 9.8, respectively. VDD [25(OH)D <50 nmol/L] prevalence was 10.3%. VDD was associated with an adjusted 6.0 (95% CI: 3.0, 9.0) and 3.4 (95% CI: 0.1, 6.6) units higher CBCL and YSR externalizing problems scores, respectively, and an adjusted 3.6 (95% CI: 0.3, 6.9) units higher CBCL internalizing problems scores. The prevalence of clinical total externalizing problems was 1.8 (95% CI: 1.1, 3.1) times higher in children with VDD than that in children without VDD. DBP concentration below the population median was related to higher YSR aggressive behavior and anxious/depressed subscale scores and to higher prevalence of clinical total externalizing problems. The associations between DBP and behavior problems were not mediated through VDD. ConclusionsVDD and low DBP in middle childhood are related to behavior problems in adolescence.

Association of thyroid cancer risk with plasma 25-hydroxyvitamin D and vitamin D binding protein: a case-control study in China.

To investigate the association of thyroid cancer (TC) with 25-hydroxyvitamin D [25(OH)D] and vitamin D binding protein (DBP) and examine whether there was an interaction between 25(OH)D and DBP in relation to TC risk. A matched case-control study based on multiple hospitals included 506 pairs of cases with newly diagnosed TC and controls. All subjects were divided into the quartiles according to the distribution of 25(OH)D and DBP in controls. Odds ratio (OR) and 95% confidence intervals (CIs) for the association of TC with 25(OH)D and DBP were estimated by conditional logistic regression. Comparing the highest to lowest quartiles, a decreased TC risk was respectively associated with plasma 25(OH)D (OR 0.63, 95% CI 0.40-1.00, P-trend = 0.046) and DBP (OR 0.49, 95% CI 0.32-0.77, P-trend = 0.001). However, the association between DBP and TC might be modified by 25(OH)D (P-interaction = 0.014) and physical activity (P-interaction = 0.017). Compared to participants with 25(OH)D and DBP concentrations respectively below medians, those with both concentrations above medians had a lower risk of TC (OR 0.56, 95% CI 0.39-0.82). In stratified analysis based on clinical characteristics of tumor, significantly negative association between 25(OH)D, and DBP and TC were observed among the cases with early stage of tumor progression. This study suggested that 25(OH)D and DBP had protective effects against TC. But the negative association between TC and DBP might be modified by 25(OH)D and physical activity.

Vitamin D binding protein and risk of renal cell carcinoma in the prostate, lung, colorectal and ovarian cancer screening trial.

Our group has conducted two previous studies on the association between vitamin D binding protein (DBP) and renal cell carcinoma (RCC), the most common form of kidney cancer, finding strong inverse associations. We undertook the current analysis to replicate our findings in a different study population that included women and nonsmokers. We conducted a nested case-control study in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO). Cases (n = 323) were matched 1:1 to controls on age (±1 year), race/ethnicity, date of blood collection (±30 days) and sex. We performed conditional logistic regression to estimate the odds ratios and 95% confidence intervals for the association between quartiles of circulating DBP and risk of RCC. We observed a statistically significant positive association between DBP and RCC that persisted after adjustment for history of diabetes, history of hypertension, family history of renal cancer, body mass index and smoking status (mv-adj Q4 vs. Q1 OR = 4.1, 95% CI = 2.2-7.8; p-trend <0.0001). These findings were similar when we restricted to cases with at least 2 years of follow-up and no major weight loss, suggesting that our findings are not due to reverse causality. In the present study, those with higher serum concentrations of DBP were at increased risk of RCC, in contrast to previously published findings. Further research is necessary to determine the true association between DBP and risk of RCC, and whether different DBP phenotypes may have different associations with risk of RCC.