Serum D Binding Protein Levels Research Articles

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).

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

Prevalence of vitamin D deficiency in women from southern Brazil and association with vitamin D-binding protein levels and GC-DBPgene polymorphisms.

Vitamin D deficiency is highly prevalent worldwide, and vitamin D-binding protein (DBP) a major regulator of serum vitamin D levels. The rs4588 and rs7041 polymorphisms of the GC gene constitute the genetic basis of the three major isoforms of circulating DBP (GC1s, GC1f, and GC2), while the rs2282679 variant is located in an important regulatory region of the GC gene. The aim of this study was to assess the prevalence of 25-hydroxyvitamin D [25(OH)D] deficiency and to ascertain whether it is associated with DBP levels and with GC gene variants. Biorepository samples of 443 women aged 20 to 72 years, with no evidence of clinical disease, were analyzed. Circulating levels of 25(OH)D were considered sufficient if ≥20 ng/mL and deficient if <20 ng/mL. Genotype analysis was performed by RT-PCR. Mean age was 53.4±9.4 years; mean BMI was 27.8±5.8 kg/m2. The overall sample had mean 25(OH)D levels of 22.8±8.3 ng/mL; 39.7% of participants had deficient circulating 25(OH)D levels. Higher prevalence ratios (PR) of 25(OH)D deficiency were found for the CC genotype of rs2282679 (PR 1.74; 95%CI 1.30 to 2.24; p<0.001), GC2 isoform (PR 1.66; 95%CI 1.17 to 2.38; p = 0.005), time since menopause (PR 1.02; 95%CI 1.003 to 1.03, p = 0.016), and HOMA-IR (PR 1.02; 95%CI 1.01 to 1.03, p = 0.004). DBP levels (per 30 μg/mL increase in DBP) were associated with lower PR for 25(OH)D deficiency (PR 0.89; 95%CI 0.80;0.99; p = 0.027). Except for HOMA-IR, these prevalence ratios remained significant after adjustment for age and BMI. In conclusion, the rs2282679 polymorphism and the GC2 isoform of DBP were associated with lower serum DBP levels and with susceptibility to 25(OH)D deficiency in Brazilian women with no evidence of clinical disease.

Comparison of free and total 25-hydroxyvitamin D in normal human pregnancy

Vitamin D status correct monitoring during pregnancy is critically important for both maternal and fetal health. 25-Hydroxyvitamin D (25(OH)D) – a prohormone of a biologically active 1,25-dihydroxyvitamin D (1,25(OH)2D), despite the lack of biological activity, during the past decades has been routinely used as a main biomarker characterizing vitamin D status. About 85% of 25(OH)D in the bloodstream is bound to its specific carrier – vitamin D-binding protein (DBP), the remaining 15% are loosely bound to albumin, and only less than 0.1% are free in the circulation (“free 25(OH)D”). Total 25(OH)D is the sum of DBP-bound, albumin-bound and free 25(OH)D. According to a “free hormone hypothesis”, only free 25(OH)D is able to induce a biological effect. Normal pregnancy is characterized by elevated serum DBP levels, and due to this fact the diagnostic strength of serum total 25(OH)D has been questioned. Free 25(OH)D might be a better characteristic of vitamin D status in this settings.We aimed to compare the diagnostic strength of a routine total 25(OH)D with directly measured free 25(OH)D in normal pregnancy by comparing the association strength between free and total 25(OH)D with biomarkers of bone health (PTH, calcium, bone-specific alkaline phosphatase (BSAP)), lipid metabolism (adiponectin, LDL, HDL), kidney function (urea), endocrine parameters (T4, T3, TSH), and group B water-soluble vitamins.The study was conducted in 368 healthy white pregnant women – residents of north-east Germany.Free 25(OH)D showed an overall better associations with gestational age, markers of bone metabolism (calcium (rho = 0.141, p = 0.007 with free 25(OH)D; rho = 0.060, p = 0.251 with total 25(OH)D) and BSAP (rho = −0.203, p < 0.001 with free 25(OH)D; rho = −0.108, p = 0.038 with total 25(OH)D), lipid metabolism parameters (adiponectin (rho = 0.142, p = 0.008 with free 25(OH)D; rho = 0.054, p = 0.307 with total 25(OH)D), LDL cholesterol (rho = −0.191, p < 0.001 with free 25(OH)D; rho = 0.033, p = 0.539 with total 25(OH)D)) and a kidney function marker (urea (rho = 0.114, p = 0.032 with free 25(OH)D; rho = 0.008, p = 0.887 with total 25(OH)D)) than total 25(OH)D.In conclusion, the current study revealed that free 25(OH)D is a more precise determinant of the vitamin D status during normal human pregnancy than total 25(OH)D. In the settings of normal pregnancy, free 25(OH)D revealed better associations with markers of bone metabolism (calcium, BSAP), lipid metabolism (adiponectin, LDL cholesterol, LDL/HDL ratio) and kidney function (urea) than total 25(OH)D.

Serum Bioavailable and Free 25-Hydroxyvitamin D Levels, but Not Its Total Level, Are Associated With the Risk of Mortality in Patients With Coronary Artery Disease.

Bioavailable and free 25-hydroxyvitamin D (25(OH)D) are emerging measurements of vitamin D. Whether serum bioavailable or free 25(OH)D level is associated with mortality in patients with coronary artery disease (CAD) is unknown. Our aim is to determine the potential association between serum total, bioavailable, and free 25(OH)D levels and the risk of mortality among patients with CAD. We measured serum 25(OH) levels in 1387 patients with angiographically confirmed CAD from the Guangdong Coronary Artery Disease Cohort. Serum DBP (vitamin D-binding protein) levels were measured using a polyclonal immunoassay, and serum-free 25(OH)D levels were measured using a 2-step immunoassay. Bioavailable 25(OH)D levels were calculated using a previously validated formula. By the median follow-up time of 6.7 years, 205 patients had died, including 134 deaths from cardiovascular diseases. In multivariate analyses, low serum bioavailable 25(OH)D level was significantly associated with increased risks of mortality, independent of established cardiovascular risk factors, features and treatments of CAD, factors associated with vitamin D and mineral metabolism, and CRP (C-reactive protein). The multivariable-adjusted hazard ratios across quartiles of bioavailable 25(OH)D were 1.79, 1.35, 1.36, and 1.00 for all-cause mortality ( P for trend=0.01) and 2.58, 1.85, 1.73, and 1.00 for cardiovascular mortality ( P for trend=0.001), respectively. Serum-free 25(OH)D level was inversely associated with the risk of mortality, with the extreme-quartile hazard ratios of 1.64 for all-cause mortality ( P for trend=0.024) and 1.97 for cardiovascular mortality ( P for trend=0.013). In contrast, serum total 25(OH)D level was not significantly associated with all-cause mortality or cardiovascular mortality. Lower serum bioavailable and free 25(OH)D levels rather than total 25(OH)D level are independently associated with an increased risk of all-cause mortality and cardiovascular mortality in a population-based CAD cohort.

Serum vitamin D and vitamin D-binding protein levels in mother-neonate pairs during the lactation period

BackgroundTo determine longitudinally the relationship between serum 25-hydroxyvitamin D (vitamin D) and vitamin D-binding protein (DBP) levels in mother-neonate pairs and evaluate the efficiency of prophylactic vitamin D on lactation days 45–60.MethodsMother-neonate pairs whose serum calcium (Ca), phosphorus (P), magnesium (Mg), alkaline phosphatase (ALP), and parathyroid hormone (PTH) levels were in normal ranges on postpartum/postnatal days 5–10 were classified into two groups by their serum vitamin D concentrations (Group A: < 10 ng/ml and Group B: > 20 ng/ml). Both maternal and neonatal Ca, P, Mg, ALP, and PTH concentrations in group A and B were not different. Maternal and neonatal serum DBP levels were measured in two groups. The mother-neonate pairs in both groups were given 400 IU/d vitamin D orally. The same biochemical markers in group A were remeasured on days 45–60 of the lactation period.ResultsIn group A, the mean maternal and neonatal vitamin D levels on postpartum/postnatal days 5–10 were significantly lower and the DBP levels were significantly higher than those in group B (P = 0.000; P = 0.000 and P = 0.04; P = 0.004, respectively). On lactation days 45–60, the maternal and neonatal DBP concentrations were not different from those on postpartum/postnatal days 5–10. However, the maternal and neonatal vitamin D levels were significantly increased (P = 0.000 and P = 0.000, respectively), while the neonatal PTH concentrations were significantly decreased (P = 0.000). The maternal and neonatal vitamin D concentrations were negatively correlated with their DBP concentrations (P = 0.048 and P = 0.002, respectively).ConclusionHigh maternal and neonatal DBP levels may lead to an incorrect low estimate of the true Vitamin D concentration. In this case, only prophylactic vitamin D (400 IU/d) is indicated for mothers and their infants.

Vitamin D-binding protein, vitamin D status and serum bioavailable 25(OH)D of young Asian Indian males working in outdoor and indoor environments.

Urban Asian Indians generally have low serum 25(OH)D. Information on serum bioavailable 25(OH)D and the effect of prolonged sun-exposure in them is not known. We assessed serum 25(OH)D and bioavailable 25(OH)D in males with varying durations of sun-exposure in Delhi during August-September. Serum 25(OH)D, vitamin D-binding protein (DBP), bioavailable 25(OH)D, free 25(OH)D index, iPTH, ionized calcium and sun-index were assessed in outdoor, mixed outdoor-indoor and indoor workers (n=88, 32 and 74, respectively). The mean sun-index (12.0±6.25, 4.3±2.20 and 0.7±0.62, respectively; P<0.001) was highest outdoors and lowest indoors. Serum 25(OH)D (29.0±8.61, 19.1±5.73 and 10.9±4.19ng/ml, respectively; P<0.001), bioavailable 25(OH)D and free 25(OH)D index were maximum in outdoor workers followed by mixed-exposure and indoor workers. Their mean serum DBP levels (241.2±88.77, 239.3±83.40 and 216.6±63.93µg/ml, respectively; P=0.12) were comparable. Mean serum iPTH was significantly lower in outdoor than indoor workers and showed inverse correlations with serum 25(OH)D, bioavailable 25(OH)D and free 25(OH)D index (r=-0.401, -0.269 and -0.236, respectively; P<0.001 in all). Daily dietary-calorie intake was higher and calcium lower in outdoor than indoor workers. On regression analysis, sun-exposure was the only significant variable, increasing serum 25(OH)D by 2.03ng/ml per hour of sun-exposure (95% confidence interval 1.77-2.28; P<0.001). Outdoor workers with prolonged sun-exposure were vitamin D-sufficient, with higher serum bioavailable 25(OH)D than the indoor workers during summer. Use of serum DBP levels did not affect the interpretation of their vitamin D status.

Vitamin D-Binding Protein in Healthy Pre- and Postmenopausal Women: Relationship with Estradiol Concentrations

To examine the relationship between endogenous serum estradiol and vitamin D-binding protein (DBP) and total, free, and bioavailable 25-hydroxyvitamin D (25OHD) concentrations in pre- and postmenopausal women. In 165 healthy women (ages, 26 to 75 years) not taking any form of exogenous estrogen, the serum concentrations of estradiol, 25OHD, DBP, parathyroid hormone, and albumin were measured. Free and bioavailable 25OHD (free + albumin-bound) levels were calculated from total 25OHD, DBP, and serum albumin levels. Premenopausal women had higher serum 25OHD (31.5 ± 7.9 ng/mL), DBP (45.3 ± 6.2 mg/dL), and estradiol (52.8 ± 35.0 pg/mL) levels than postmenopausal women (26.5 ± 4.9 ng/mL, 41.7 ± 5.7 mg/dL, and 12.9 ± 4.9 pg/mL), respectively. In addition, the calculated free and bioavailable 25OHD levels were higher in pre- than postmenopausal women (P<.05). Serum estradiol correlated with DBP (r = 0.22; P<.01) and total 25OHD (r = 0.27; P<.01). In multivariate regression models (with or without serum 25OHD), estradiol was independently associated with DBP (P<.05). Lower estradiol level is one of the factors that contribute to lower DBP levels in older women. Our data indicate that besides well-known factors such as age, gender, and race, serum estradiol concentrations are also a physiologic predictor of DBP concentration.

Vitamin d binding protein and vitamin d levels.

Over the past few decades, there has been a growing interest in understanding the multifunctional characteristics and clinical importance of vitamin D binding protein (DBP). Multiple studies have shed light on DBP, giving rise to hopes of identifying novel mechanisms as well as utilizing DBP as a potential therapeutic agent. The current issue is comprised of 6 manuscripts, two of which are review articles. The areas covered in this special issue mostly highlight the potential role of DBP in several conditions including periodontitis and frailty, implying that measurement of DBP may provide useful information in addition to total 25-hydroxy vitamin D concentration. In this issue, the review by P. Yousefzadeh et al. titled “Vitamin D binding protein impact on 25-hydroxyvitamin D levels under different physiologic and pathologic conditions” calls for the implementation of DBP testing during the interpretation of 25-hydroxyvitamin D [25(OH)D] results under different clinical situations. I. Bhan reviews the recent findings regarding the association between the differences in vitamin D binding protein levels and bone density in his paper titled “Vitamin D binding protein and bone health.” The author has compiled studies concerned with DBP, including DBP polymorphisms in relation to bone health and its association with vitamin D bioavailability. These findings may impact not only strategies for designing novel therapeutic agents that influence DBP or its binding, but also our understanding of the mechanism of vitamin D in the context of bone health. Evidence is emerging that the DBP polymorphisms are associated with race and ethnicity, resulting in differences in DBP levels and binding affinity that affect the transport and metabolism of vitamin D and its metabolites. Using serum samples from various populations with varying DBP levels, J. Freeman et al., in their paper titled “Influence of vitamin D binding protein on accuracy of 25-hydroxyvitamin D measurement using the ADVIA Centaur vitamin D total assay,” assessed the agreement between the ADVIA Centaur vitamin D total assay for 25(OH)D testing and the liquid chromatography mass spectrometry (LS-MS/MS) method and concluded that the ADVIA Centaur vitamin D total assay demonstrated good performance compared to the LS-MS/MS method across the normal range of DBP concentrations. This is one example of methods development in the field to ensure accurate and simpler protocols for measuring circulating 25(OH)D in future study. X. Zhang et al., in their paper titled “Vitamin D-binding protein levels in plasma and gingival crevicular fluid (GCF) of patients with generalized aggressive periodontitis,” examined the association of DBP with generalized aggressive periodontitis (GAgP). The authors found that GAgP patients had higher plasma DBP concentrations but lower GCF DBP concentrations than healthy controls, suggesting that decreased GCF-DBP level and increased plasma DBP level are associated with periodontitis. This study adds to the growing evidence of the potential role of DBP in the pathogenesis of periodontitis. Existing evidence shows an association of high circulating 25(OH)D levels with low TSH levels in younger individuals, but there is insufficient information on whether it is the same in the elderly and middle-aged. Q. Zhang et al., in their paper titled “Association of high vitamin D status with low circulating thyroid-stimulating hormone independent of thyroid hormone levels in middle-aged and elderly males,” report that such an association does exist in middle-aged and elderly males, independent of thyroid hormone levels. The authors also demonstrated the link between vitamin D insufficiency and serum thyroid antibody levels. Y. Wang et al., in their paper entitled “Vitamin D binding protein affects the correlation of 25(OH)D and frailty in the older men,” assessed the frailty status in elderly men of Changsha city, China, and concluded that serum DBP levels should be measured when evaluating the 25(OH)D- frailty relationship. We hope that these articles convey new insights to readers and researchers into the current renewed interest in vitamin D and DBP research. Zhongjian Xie Arthur C. Santora Sue A. Shapses Xiangbing Wang

Influence of Vitamin D Binding Protein on Accuracy of 25-Hydroxyvitamin D Measurement Using the ADVIA Centaur Vitamin D Total Assay

Vitamin D status in different populations relies on accurate measurement of total serum 25-hydroxyvitamin D [25(OH)D] concentrations [i.e., 25(OH)D3 and 25(OH)D2]. This study evaluated agreement between the ADVIA Centaur Vitamin D Total assay for 25(OH)D testing (traceable to the NIST-Ghent reference method procedure) and a liquid chromatography tandem mass spectrometry (LC-MS/MS) method for various populations with different levels of vitamin D binding protein (DBP). Total serum 25(OH)D concentrations were measured for 36 pregnant women, 40 hemodialysis patients, and 30 samples (DBP-spiked or not) from healthy subjects. ELISA measured DBP levels. The mean serum DBP concentrations were higher for pregnancy (415 μg/mL) and lower for hemodialysis subjects (198 μg/mL) than for healthy subjects and were highest for spiked serum (545 μg/mL). The average bias between the ADVIA Centaur assay and the LC-MS/MS method was −1.4% (healthy), −6.1% (pregnancy), and 4.4% (hemodialysis). The slightly greater bias for samples from some pregnancy and hemodialysis subjects with serum DBP levels outside of the normal healthy range fell within a clinically acceptable range—reflected by analysis of their low-range (≤136 μg/mL), medium-range (137–559 μg/mL), and high-range (≥560 μg/mL) DBP groups. Thus, the ADVIA Centaur Vitamin D Total assay demonstrates acceptable performance compared with an LC-MS/MS method for populations containing different amounts of DBP.

Vitamin D Binding Protein Affects the Correlation of 25(OH)D and Frailty in the Older Men.

Vitamin D binding protein (DBP) may alter the biologic activity of 25-hydroxyvitamin D [25(OH)D]. The objective of our present study was to determine the joint effect of serum 25(OH)D and DBP on the risk of frailty. Five hundred sixteen male participants aged 70 years or older were recruited in Changsha city and its surrounding area in Hunan province of China. Frailty was defined as the presence of at least three of the five following criteria: weakness, low physical activity, slow walking speed, exhaustion, and weight loss. Multivariate linear regression analysis was performed to assess the relationship between 25(OH)D and DBP levels. Odds ratios (ORs) for frailty were evaluated across quartiles of 25(OH)D and DBP levels, adjusted age, education, and body mass index. The results showed that participants in the lowest quartile of 25(OH)D and the highest quartile of DBP levels, the lowest quartile of 25(OH)D and the lowest quartile of DBP levels, and those in the the lower quartile of 25(OH)D and lowest quartile of DBP levels had significantly higher OR of being frail compared with those in the highest quartile of 25(OH)D and lowest quartile of DBP, with OR of 3.18 (95% CI: 1.46–4.56, P < 0.05), 2.63 (95% CI: 1.31–3.68, P < 0.01), and 2.52 (95% CI: 1.22–3.52, P < 0.05), respectively. The results indicate that the joint effect of serum 25(OH)D and DBP levels is associated with the risk of frailty, and serum DBP levels affects 25(OH)D-frailty relationship in the older men.

Circulating DBP level and prognosis in operated lung cancer: an exploration of pathophysiology

Vitamin D stimulates transcription of antiangiogenic and apoptotic factors that may suppress tumours, while vitamin D binding protein (DBP) may be a biomarker in murine lung cancer models. We sought to ascertain whether the vitamin D axis is altered in lung cancer or influences prognosis. 148 lung cancer patients, 68 other intrathoracic cancer patients and 33 noncancer controls were studied for up to 5 yrs. Circulating DBP and vitamin D levels were compared between groups and their effect on survival assessed by Cox regression analysis. Expression of DBP and vitamin D receptor (VDR) was examined in lung cancer cell lines and in normal and tumour lung tissue by Western blot and immunohistochemistry. Low serum DBP levels predicted lung cancer-specific death (p=0.04), and DBP was poorly expressed in lung cancer cells on Western blot and immunohistochemistry. Vitamin D did not predict cancer survival and VDR expression was variable in tumours. Preservation of serum DBP is a significant independent factor associated with better cancer outcome in operated lung cancer patients. Given the established role of DBP in macrophage activation and clearance of abnormal cells, further study on its involvement in lung cancer is merited.

Vitamin D metabolites in childhood nephrotic syndrome.

We measured serum levels of total and ionised calcium, phosphate, intact parathyroid hormone, 25-hydroxyvitamin D [25(OH)D], 1,25-dihydroxyvitamin D [1,25(OH)2D] and the vitamin D binding protein (DBP) in 14 children with idiopathic nephrotic syndrome and 10 healthy, age-matched controls. In all nephrotics serum DBP levels were below the normal range. Serum 25(OH)D was below 7 ng/ml in 10 of 14 nephrotic children and in the low normal range in the remaining 4 patients. The average serum 1,25(OH)2D levels were lower in the nephrotic patients than in the controls. However, free 1,25(OH)2D levels were normal in the nephrotic patients. Both serum 25(OH)D and 1,25(OH)2D correlated positively with the concentration of DBP. There was a significant negative correlation between serum DBP levels and the urinary protein excretion and a significant positive correlation between the urinary excretions of DBP and albumin. From this study it can be concluded that the nephrotic child is capable of maintaining appropriate serum concentrations of free calcitriol despite important urinary losses of both substrate and bound calcitriol.

Serum concentrations of 25-hydroxyvitamin D and vitamin D-binding protein in elderly people. Effects of institutionalization, protein-energy malnutrition and inflammation.

Serum concentrations of 25-hydroxyvitamin D (25-OH-D) and vitamin D-binding protein (DBP) were measured in institutionalized and non-institutionalized elderly people. The institutionalized subjects were found to have low serum 25-OH-D in confirmation of other studies, but their serum DBP levels were similar to those found in non-institutionalized elderly subjects. Serum DBP concentrations were slightly higher in elderly females than in males, while no age dependence was found for DBP. Elderly people with protein-energy malnutrition who lived in their own homes had slightly reduced serum DBP and 25-OH-D levels. Elderly subjects with infections or other diseases causing acute inflammation, as indicated by an elevated serum haptoglobin and C-reactive protein, had normal levels of DBP.