Serum Vitamin D-binding Protein Research Articles

Association of Serum Vitamin D-binding Protein with Components of Metabolic Syndrome in Type 2 Diabetic Patients in Gorgan

Association of Serum Vitamin D-binding Protein with Components of Metabolic Syndrome in Type 2 Diabetic Patients in Gorgan

Tip 1 Diyabette Serum Vitamin D Bağlayan Protein Düzeylerinin Araştırılması: Glisemik Kontrol ve Hastalık Süresinin Etkisi

Aim: Patients with type 1 diabetes mellitus (T1DM) are known to be more prone to vitamin D deficiency. Vitamin D studies in this
 patient population have traditionally been performed using serum 25OHD levels. However, vitamin D binding protein (VDBP) has
 been less studied. This study aims to compare serum VDBP levels in T1DM with healthy controls. It also aims to investigate the factors
 affecting VDBP levels such as disease duration, HbA1c, insulin dose, and age in diabetic subjects.
 Material and Methods: A research study was conducted at Çanakkale Onsekiz Mart University Health Practice and Research Hospital.
 The study included 11-17 years old children with T1DM and healthy controls. Serum VDBP and 25OHD concentrations were compared
 with appropriate statistical methods according to the normal distribution of relevant parameters. For the diabetic subjects, insulin doses
 and duration of diabetes were recorded. Spearman’s correlation test was utilized to assess associations between continuous variables, and
 regression analysis was employed to determine predictors of serum VDBP levels.
 Results: The study enrolled 89 subjects, including 40 with diabetes. Serum 25OHD levels were similar in the T1DM group and control
 group (17.03 IQR:12.89-22.08) and (17.62 IQR:11.68-24.48), respectively (p=0.701). However, VDBP levels were significantly lower in
 the T1DM group (335 μg/ml, IQR: 199.8-517.2 μg/ml) compared to the control group (471.2 μg/ml, IQR: 368.3-533.2 μg/ml) (p < 0.015).
 In the entire group, only the presence of diabetes affected VDBP levels (B=87.236, SE=34.802, p=0.014). On the other hand, HbA1c,
 duration of diabetes, and insulin dose had no influence on VDBP in the diabetes group.
 Conclusion: Serum VDBP levels were significantly lower in T1DM patients but in this group, disease duration, insulin dose, and
 metabolic control did not affect serum VDBP levels. Serum VDBP concentrations in T1DM may be affected by other parameters rather
 than metabolic parameters. Therefore, future studies should focus on addressing this knowledge gap.

Genetic influence on urinary vitamin D binding protein excretion and serum levels: a focus on rs4588 C>A polymorphism in the GC gene.

Vitamin D binding protein (VDBP) plays a crucial role in vitamin D transport and metabolism. The rs4588-A polymorphism of the GC gene, encoding VDBP, has been associated with altered serum VDBP and 25-hydroxyvitamin D (25OHD) levels. However, the mechanisms underlying these effects remain unclear. We aimed to investigate the relationship between urinary VDBP excretion and serum VDBP and 25OHD levels in individuals with and without the rs4588-A allele. A cross-sectional study was conducted on 109 children (mean age: 11.96 years) to explore the impact of rs4588-A on vitamin D metabolism and urinary VDBP excretion. Biochemical analyses determined serum 25OHD and VDBP levels, and urinary VDBP-to-creatinine ratio (u-VDBP/Cr). Genotyping for rs4588 SNP was performed using LightSNiP assay. Statistical analyses included correlation, linear regression, and comparison between allele groups. Participants carrying the rs4588-A allele exhibited lower serum 25OHD levels compared to non-carriers (median (IQR): 11.85 (3.5) vs. 12.86 (4.9), p = 0.023). However, no statistically significant differences were observed in serum VDBP levels (126.34 ± 59.3 in rs4588-A vs. 136.49 ± 51.3 in non-rs4588-A, p = 0.141) or in u-VDBP/Cr (median (IQR): 0.4 (0.35) in rs4588-A vs. 0.386 (0.43) in non-rs4588-A, p = 0.189) between the two allele groups. A significant inverse correlation between u-VDBP/Cr and serum VDBP levels was found only in rs4588-A carriers (r = -0.367, p = 0.024). No such correlation was observed in non-carriers or the entire cohort. A linear regression analysis confirmed the impact of u-VDBP/Cr on serum VDBP levels in rs4588-A carriers (B = -0.269, t = -2.185, p = 0.035). Individuals with the rs4588-A allele in the GC gene had lower serum 25OHD levels. An inverse correlation between urinary VDBP excretion and serum VDBP levels was observed, suggesting a partial role of the renal pathway in altered serum VDBP and 25OHD levels linked to the rs4588-A allele.

Metabolism of vitamin D is not affected by sport activity

BackgroundHigher levels of physical activity are related to higher 25-(OH)D levels. Total 25-(OH)D (25-(OH)DT) are routinely used in clinical practice to assess vitamin D, however novel biomarkers are currently being investigated as free 25-(OH)D (25-(OH)DF) or vitamin D metabolite ratios (VMRs). The primary aim of our study was to assess 25-(OH)DF, vitamin D metabolites and VMRs in inactive men and athletes. A secondary aim was to check whether regular physical activity influence on vitamin D metabolome. A tertiary aim was to determine the relationship between 25-(OH)DT, 25-(OH)DF, vitamin D binding protein (VDBP), vitamin D metabolites and VMRs in this cohort. MethodsA total of 69 participants (27 inactive men, 18 indoor and 24 outdoor athletes) participated in the study. Vitamin D metabolites (25-(OH)DT, 24,25-(OH)2D3, 3-epi-25-(OH)D3, and 1,25-(OH)2D) were assessed using LC-MS/MS. The 25-(OH)DF concentration was calculated based on serum albumin and VDBP levels. ResultsThere were no differences in vitamin D metabolites and VMRs between inactive men and between the two groups of athletes. We showed a strong relationship between 25-(OH)DT, 25-(OH)DF and 24,25-(OH)D3, 3-epi-25(OH)D3, 24,25-(OH)2D3:25-(OH)D3 VMR in each group. Analysis showed that 25-(OH)DT, 25-(OH)DF inversely associated with 25-(OH)D3:24,25-(OH)2D3, 25-(OH)D3:3-epi-25-(OH)D3, 1,25-(OH)2D:24,25-(OH)2D3 ratios in inactive men and athletes (indoor and outdoor). ConclusionsOn the basis of our results, we concluded that regular long-term physical activity has no effect on the concentration of vitamin D metabolites at rest. Furthermore, free vitamin D does not correlate more strongly with vitamin D metabolites and VMRs compared to total.

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.

Genome-wide association study (GWAS) of circulating vitamin D outcomes among individuals of African ancestry

BackgroundVitamin D deficiency is more common among African-ancestry individuals and may be associated with adverse health outcomes. Vitamin D binding protein (VDBP) regulates concentrations of biologically active vitamin D. ObjectiveWe conducted genome-wide association study (GWAS) of VDBP and 25-hydroxyvitamin D among African-ancestry individuals. MethodsData were collected from 2,602 African American adults from the Southern Community Cohort Study (SCCS) and 6,934 African- or Caribbean-ancestry adults from the UK Biobank. Serum VDBP concentrations were available only in the SCCS and were measured by using the Polyclonal Human VDBP ELISA kit. Serum 25-hydroxyvitamin D concentrations for both study samples were measured by using Diasorin Liason, a chemiluminescent immunoassay. Participants were genotyped for single nucleotide polymorphisms (SNPs) with genome-wide coverage by using Illumina or Affymetrix platforms. Fine-mapping analysis was performed by using forward stepwise linear regression models including all variants with P value < 5 × 10−8 and within 250 kbps of a lead SNP. ResultsWe identified 4 loci notably associated with VDBP concentrations in the SCCS population: rs7041 (per allele β = 0.61 μg/mL, SE = 0.05, P = 1.4 × 10−48) and rs842998 (per allele β = 0.39 μg/mL, SE = 0.03, P = 4.0 × 10−31) in GC, rs8427873 (per allele β = 0.31 μg/mL, SE = 0.04, P = 3.0 × 10−14) near GC and rs11731496 (per allele β = 0.21 μg/mL, SE = 0.03, P = 3.6 × 10−11) in between GC and NPFFR2. In conditional analyses, which included the above-mentioned SNPs, only rs7041 remained notable (P = 4.1 × 10−21). SNP rs4588 in GC was the only GWAS-identified SNP associated with 25-hydroxyvitamin D concentration. Among UK Biobank participants: per allele β = −0.11 μg/mL, SE = 0.01, P = 1.5 × 10−13; in the SCCS: per allele β = −0.12 μg/mL, SE = 0.06, P = 2.8 × 10−02). rs7041 and rs4588 are functional SNPs that influence the binding affinity of VDBP to 25-hydroxyvitamin D. ConclusionsOur results were in line with previous studies conducted in European-ancestry populations, showing that GC, the gene that directly encodes for VDBP, would be important for VDBP and 25-hydroxyvitamin D concentrations. The current study extends our knowledge of the genetics of vitamin D in diverse populations.

Serum Vitamin D Biomarkers in Pregnant Women with Preeclampsia: A Prospective Pilot Study

Background: It has been suggested that hypovitaminosis D is associated with the development of preeclampsia. This study aimed to study the relationship between preeclampsia and various vitamin D serum biomarkers including 25-hydroxyl vitamin D [25(OH)D], vitamin D-binding protein (VDBP), and bioavailable and free 25(OH)D. Methods: This prospective study was conducted with 17 patients with preeclampsia and 38 normal pregnant women as the control group. Total serum 25(OH)D and VDBP concentrations were measured. The levels of bioavailable 25(OH)D and free 25(OH)D were also calculated. Two single nucleotide polymorphisms (rs4588 and rs7041) of the GC gene encoding VDBP were analyzed. Results: VDBP was significantly increased in the preeclampsia group compared to the normal pregnancy group (454.2 vs. 403.4 ng/mL; p = 0.036). When the preeclampsia patients were analyzed by dividing them into early-onset and late-onset, there was no significant difference in the serum vitamin D biomarkers levels. Also, when preeclampsia patients were classified into three subgroups of &lt;2 days, 2–7 days, and &gt;7 days from diagnosis to delivery, free 25(OH)D concentrations were significantly increased in the 2–7 days subgroup compared to the other subgroups (3.5 vs. 6.6 vs. 3.1 pg/mL; p = 0.032). The GC genotype and allele frequency showed no statistically significant different distribution between the preeclampsia and normal pregnancy groups. Conclusions: In the present study, the serum VDBP levels were significantly higher in the patients with preeclampsia than in the normal pregnancy group. Thus, among various serum vitamin D biomarkers, increased VDBP could be associated with the onset and pathogenesis of preeclampsia.

Unravelling the Contribution of the rs7041 and rs4588 Polymorphisms of the GC Gene and Serum VDBP Levels for Developing Metabolic Syndrome in the Mexican Population.

Metabolic syndrome (MetS) is a multifactorial disorder integrated by a constellation of cardiovascular risk factors. The genetic and environmental determinants of MetS are not fully elucidated. This study investigated the association of two common single nucleotide polymorphisms (SNPs) on GC, rs7041 and rs4588, derived haplotypes, and serum vitamin D binding protein (VDBP) levels with the susceptibility to suffer MetS in Mexican adults. We included 1924 individuals; clinical and biochemical data were obtained through standard methods. Genotyping was performed through predesigned TaqMan assays. Logistic regression models were used to assess the associations of interest. Prevalence of MetS was 52.9% in the whole population, being more frequent in women. We observed that some association results differed between sexes. The GG genotype of the rs7041 was associated with increased odds of MetS in women. For the rs4588, the CA genotype had a protective effect against MetS in women. The haplotype GC2 was associated with reduced odds for MetS and some of its components in women. Our data suggest that VDBP serum levels were influenced by genotypes/haplotypes and this interplay seems to influence the risk of MetS. Our data provide reliable evidence regarding the association of GC polymorphisms with MetS risk in Mexican women.

Vitamin D, Vitamin D-Binding Proteins, and VDR Polymorphisms in Individuals with Hyperglycaemia.

Vitamin D reportedly plays an important role in the pathogenesis of diabetes mellitus; however, this role is unclear and debated. This study investigated the association between 25(OH) vitamin D, vitamin D-binding proteins, and vitamin D receptor (VDR) polymorphisms in healthy individuals and those with prediabetes and type 2 diabetes mellitus (T2D) from South Africa. A cross-sectional study was conducted involving subjects of mixed ancestry aged ≥20 years. Males presented with higher mean 25(OH) vitamin D levels than females, while females exhibited significantly higher serum vitamin D-binding protein levels. Significant differences in mean 25(OH) vitamin D levels were observed in normo-glycaemic, prediabetes, screen-detected DM, and known DM individuals. Vitamin D receptor SNPs Fok1 and Taq1 were not associated with glycaemic status. Fok1 was not associated with 25(OH) vitamin D deficiency, while Taq1 was associated with vitamin D insufficiency. This study showed a high prevalence of vitamin D deficiency/insufficiency in this South African population, with decreased vitamin D levels observed in hyperglycaemic individuals, which was not linked to either vitamin D-binding protein or polymorphisms in Fok1 of the VDR gene. These results may be used as a platform for further research into diagnosis and treatment of hyperglycaemia.

The association of vitamin D binding protein levels and genotypes with type 1 diabetes in the black South African population

BackgroundVitamin D deficiency and the vitamin D pathway have previously been associated with type 1 diabetes (T1D). The majority of vitamin D is transported through the blood bound to the vitamin D binding protein (VDBP). Two polymorphisms in the VDBP gene (rs4588 and rs7041) result in different VDBP variants and have been associated with T1D, however the results are not consistent. The association of VDBP levels and its polymorphisms with T1D have not been investigated in the black South African population. Therefore, this study aimed to determine whether rs4588, rs7041 or serum VDBP levels were associated with T1D in this population.MethodsParticipants with type 1 diabetes and controls were recruited from the greater Johannesburg area, South Africa. Participants were genotyped for rs4588 and rs7041 using PCR-RFLP and serum VDBP levels were determined by ELISA.ResultsThere was no difference in VDBP allelic or genotypic frequencies between participants with T1D and controls (rs4588 C allele frequency 0.92 vs. 0.94; p = 0.390 and rs7041 T allele frequency 0.95 vs. 0.95; p = 0.890). In univariate analysis, the rs4588 CC genotype was associated with increased serum VDBP levels, however, this association was lost with multivariate analysis. The VDBP genotypes were not associated with any other study variables. In logistic regression analysis, higher VBDP levels were associated with T1D (OR: (95% CI): 6.58 (1.45–29.9); p = 0.015), and within a linear regression analysis, T1D disease status was found to be associated with 0.044 mg/ml higher VDBP levels (p = 0.028).ConclusionsThese data suggest that serum VDBP levels are positively associated with the presence of T1D in the African population. Whether VDBP lies in the causal pathway or its elevation is an effect of T1D is uncertain and requires further investigation.

Relationship Between Metabolites of Vitamin D, Free 25-(OH)D, and Physical Performance in Indoor and Outdoor Athletes.

The potential effects of vitamin D in athletes have received considerable attention in the literature. However, little is known about vitamin D metabolites and their association with physical performance in athletes. Therefore, the aim of our study was to determine the relationship between metabolites of vitamin D, vitamin D binding protein (VDBP), free, bioavailable 25-(OH)D, and physical fitness tests in athletes. A total of 40 indoor and outdoor players (16 judoists and 24 football players) participated in the study. Vitamin D metabolites (25-(OH)D, 24,25-(OH)2D3, 3-epi-25-(OH)D3, and 1,25-(OH)2D) were assessed using LM-MS/MS. Free 25-(OH)D concentration was evaluated by calculation using serum albumin and VDBP levels. Athletic performance was assessed using handgrip and vertical jump. Our study showed a significant correlation between vitamin D metabolites and handgrip strength and vertical jump variables in indoor players. It demonstrated a significant association between 3-epi-25-(OH)D3 and vertical jump parameters in outdoor players. The results of our study showed relationship between free, bioavailable 25-(OH)D, and vertical jump variables in indoor players. In conclusion, we provide novel information on the vitamin D metabolites and athletic performance in athletes. Based on the results of our study, we concluded that vitamin D metabolites might be involved in skeletal muscle function in relation to athletic performance.

Leukocyte telomere length as a compensatory mechanism in vitamin D metabolism.

Vitamin D deficiency is common among postmenopausal women. Telomere length can be a potential protective mechanism for age-related diseases. The objective of our study is to examine the association of vitamin D supplementation on leukocyte telomere length (LTL) in healthy postmenopausal women with vitamin D deficiency. The study was designed as a placebo-controlled study to investigate the short-term effects of vitamin D supplementation and seasonal changes on vitamin D related parameters, including 25(OH)D, 1,25(OH)2D parathormone (PTH), Vitamin D binding protein (VDBP), vitamin D receptor (VDR), and telomere length in a cohort of postmenopausal women (n = 102). The group was divided as supplementation (n = 52) and placebo groups (n = 50). All parameters were measured before and after treatment. Serum VDBP levels were measured by ELISA method and VDR, GC (VDBP) gene expressions and relative telomere lengths were measured in peripheral blood mononuclear cells (PBMC) using a quantitative real-time PCR method. The results demonstrate that baseline levels were similar between the groups. After vitamin D supplementation 25(OH)D, 1,25(OH)2D, PTH and VDBP levels were changed significantly compared to the placebo group. At the end of the study period, LTL levels were significantly increased in both groups and this change was more prominent in placebo group. The change in GC expression was significant between treatment and placebo groups but VDR expression remained unchanged. Even though the study was designed to solely assess the effects of vitamin D supplementation, LTL was significantly increased in the whole study group in summer months suggesting that LTL levels are affected by sun exposure and seasonal changes rather than supplementation. The study displayed the short-term effect of Vitamin D supplementation on vitamin D, PTH levels, LTL and vitamin D associated gene expressions. The relation between Vitamin D and LTL is not linear and could be confounded by several factors such as the population differences, regional and seasonal changes in sun exposure.

Serum vitamin D-binding protein (VDBP) concentration and rs7041 genotype may be associated with preterm labor

Purpose Vitamin D deficiency is common during pregnancy and may cause complications such as preterm labor (PTL). This study was aimed to investigate the effect of the vitamin D-binding protein (VDBP) rs7041 genotype, which has a significant effect on vitamin D metabolism and PTL. Methods This cross-sectional study was conducted with 32 pregnant women who had spontaneous PTL and 54 pregnant women who had no specific findings as a control group. Serum total vitamin D 25-hydroxy vitamin D (25(OH)D) levels were measured using the Elecsys Vitamin D Total Kit. VDBP was measured using a VDBP Quantikine ELISA Kit. The levels of bioavailable 25(OH)D were calculated based on the total 25(OH)D and VDBP concentrations. DNA was extracted using the DNeasy Blood and Tissue Kit. Single nucleotide polymorphisms (rs7041) in GC were analyzed using a TaqMan SNP Genotyping Assay Kit. The unpaired t-test, Chi-squared, and ANCOVA tests were performed. Firth’s penalized logistic regression was applied. The area under the curve (AUC) was calculated and the cutoff value was determined. All statistical analyses were performed using R version 4.0.3 (R Foundation for Statistical Computing, Vienna, Austria). Results Total 25(OH)D levels were not significantly different between the two groups. Bioavailable 25(OH)D was significantly decreased in PTL women (p= .011), and VDBP was significantly increased in PTL women (p= .004) compared to the controls. Bioavailable 25(OH)D was lower in women with GT/TG and TT rs7041 genotypes than in those with GG, with statistical significance in women with the TT allele (p= .048). VDBP was higher in women with GT/TG and TT than those with GG, but there was no statistical significance. In PTL prevalence, bioavailable 25(OH)D and VDBP, the odds ratio increased by 1.463 times in GT/TG (p= .728) and increased by 1.675 times in TT compared to the GG allele (p= .640). In receiver operating characteristic (ROC) analysis for bioavailable 25(OH)D and VDBP, the AUC was 0.665 and 0685, respectively. The optimum cutoff of bioavailable 25(OH)D and VDBP levels for the diagnosis of PTL was calculated as 0.6 ng/mL and 523 µg/mL, respectively. Conclusions Pregnant women with the VDBP rs7041(c.1296 T > G) T allele genotype had reduced serum levels of bioavailable 25(OH)D and were more likely to develop PTL. Therefore, if the T allele is found in the VDBP rs7041 SNP genotyping test before or during pregnancy, more careful prenatal care may be required because of the increased risk of PTL.

Potential roles of vitamin D binding protein in attenuating liver injury in sepsis

BackgroundIn sepsis, vitamin D binding protein (VDBP) has been shown to be low-expressed. The current study examined the relationship between serum VDBP level and liver injury in sepsis patients, as well as in a mouse model for sepsis and in cultured liver epithelial cell line exposed to lipopolysaccharide (LPS).MethodsThe human study included 78 sepsis patients and 50 healthy volunteers. Sepsis patients were categorized into sepsis survivor group (n = 43) and sepsis non-survivor group (n = 35) based on 28-day mortality for data analysis. Adult male C57BL/6 mice were subjected to cecal ligation and puncture (CLP). Serum samples were collected on day 1, 3, 5 and 7 to determine the levels of VDBP, 25-hydroxyvitamin D [25(OH)D3], 1,25-dihydroxyvitamin D [1,25(OH)2D3], interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α). Potential protective effects of VDBP overexpression against LPS-induced liver damage were examined in cultured THLE2 cells.ResultsSerum levels of VDBP, 25(OH)D3, and 1,25(OH)2D3 were significantly lower in sepsis patients vs. the healthy control (P < 0.001), as well as in the sepsis non-survivor group vs. the sepsis survivor group (P < 0.001, P = 0.0338, or P = 0.0013, respectively). Lower serum VDBP level was associated with higher Acute Physiology and Chronic Health Evaluation (APACHE) II score (r = − 0.2565, P = 0.0234) and Sequential Organ Failure Assessment score (r = − 0.3522, P = 0.0016), but lower serum albumin (ALB, r = 0.4628, P < 0.001) and total protein (TP, r = 0.263, P = 0.02). In CLP mice, there was a 5-day period of serum VDBP reduction, followed by return towards the baseline on day 7. VDBP was also decreased in LPS-treated THLE2 cells (P < 0.001). VDBP overexpression reduced LPS-induced THLE2 damage. Reduced damage was associated with decreased oxidative stress and inactivation of the c-Jun N-terminal kinase signaling pathway.ConclusionVDBP may be protective against sepsis-induced liver injury.

Impact of Etanercept on Vitamin D Status and Vitamin D-binding Protein in Bio-naïve Patients with Psoriasis.

High levels of serum vitamin D-binding protein have been shown previously in patients with psoriasis compared with healthy controls; a possible role in inflammation is implied. The primary objective of this study was to investigate the impact of 24-week etanercept treatment on vitamin D status and vitamin D-binding protein in patients with psoriasis. The secondary aim was to explore whether pre-treatment vitamin D levels could predict the treatment effect. A prospective observational study was performed, including 20 patients with psoriasis and 15 controls. Serum samples were analyzed for, among others, vitamin D metabolites, vitamin D-binding protein and highly sensitive Creactive protein. Baseline levels of vitamin D-binding protein were higher in patients with self-reported arthropathy than in those without. After 24 weeks’ treatment, an improvement in psoriasis was noted, as was a decrease in highly sensitive C-reactive protein. Vitamin D-binding protein decreased in those with self-reported arthropathy. Higher baseline levels of vitamin D were associated with faster and greater improvement in psoriasis. Vitamin D-binding protein may have an inflammatory biomarker role.

Correlational analysis of bone health status and vitamin D-related biomarkers in women working in agriculture.

The purpose of this study was to investigate the status of bone health in women working in agriculture and analyze the associations between bone health and various vitamin D-related biomarkers.This observational study enrolled women working in agriculture (n = 210) and control occupations (n = 180). The concentration of serum total 25-hydroxy vitamin D [25(OH)D] was measured using the Elecsys Vitamin D Total Kit, and serum vitamin D-binding protein (VDBP) was measured by enzyme-linked immunosorbent assay. Along with albumin, 25(OH)D and VDBP were used to calculate the concentrations of bioavailable and free 25(OH)D. Bone mineral density (BMD) and T-score were measured at lumbar 1 to 4 and the femur neck using dual-energy X-ray absorptiometry. To identify factors affecting BMD, log-linear model and linear regression analysis were performed for statistical analysis.Agricultural women workers showed higher serum concentrations of bioavailable 25(OH)D (12.8 ± 3.7 vs 8.7 ± 5.1 ng/mL) and lower VDBP concentrations (201.8 ± 45.0 vs 216.0 ± 68.2 μg/mL) than control women. The association between these 2 vitamin D related-biomarkers and femur neck BMD were confirmed through univariable and multivariable linear model analysis. Although lumbar BMD did not differ between groups, the agricultural group displayed a lower femur BMD and a 4.3-fold increase in the risk of osteoporosis compared with the control group.Women working in agriculture showed lower femur BMD than the control group. Of the vitamin D-related biomarkers tested, bioavailable 25(OH)D and VDBP were associated with BMD. As bioavailable 25(OH)D levels are affected mainly by VDBP levels, VDBP may play a role in the lower femur neck BMD values observed in the agricultural group. Thus, the measurement of VDBP concentration might be considered a simple and non-invasive method for measuring bone health status.

Association of GC Variants with Bone Mineral Density and Serum VDBP Concentrations in Mexican Population.

Vitamin D-binding protein (VDBP) is encoded by the GC gene and is an active participant in the control of bone metabolism. However, the effect of its major variants on VDBP concentration and bone mineral density (BMD) remains unclear. Our aim was to analyze the effect of major GC variants on serum VDBP concentration and BMD. We recruited individuals from the Health Workers Cohort Study, which includes employees of the Mexican Institute of Social Security (IMSS). A total of 1853 adults were included. The single nucleotide polymorphisms (SNPs) rs7041 and rs4588 were genotyped to identify the three best characterized haplotypes of GC. Serum VBDP, 25(OH)D and BMD were also measured. Among women, the G allele of rs7041 was associated with higher VDBP and BMD compared to homozygous TT. The A allele of rs4588 was associated with lower VDBP and BMD compared to CC homozygous. In men, GC variants were only associated with VDBP levels. We did not observe an association between free/bioavailable 25(OH)D and BMD in men and women. Our results support an association of VDBP in bone health. The G and C alleles, from rs7041 and rs4588, respectively, are associated with high concentrations of VDBP and BMD in this sample of Mexican postmenopausal women.

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.

Serum vitamin D and vitamin-D-binding protein levels in children with chronic hepatitis B.

BACKGROUNDVitamin D is an essential fat-soluble secosteroid hydroxylated by the liver to form the intermediate metabolite calcidiol {25-hydroxy vitamin D [25(OH)D]}, which is a reliable indicator to investigate individual vitamin D status. Vitamin-D-binding protein (VDBP) is a multifunctional glycoprotein mainly synthesized in the liver and the major transport protein for vitamin D and its metabolites. Serum vitamin D and VDBP are both associated with hepatitis B. However, few studies have reported the relationship and clinical significance of vitamin D and VDBP with hepatitis B virus (HBV) replication and hepatic fibrosis in children with chronic hepatitis B (CHB).AIMTo explore vitamin D and VDBP serum levels in children with CHB and the association of vitamin D and VDBP with HBV replication and hepatic fibrosis.METHODSWe enrolled 204 children with CHB admitted to Hunan Children’ Hospital in summer and autumn between 2018 and 2019 and 170 healthy controls. CHB patients included: 164 hepatitis B e antigen (HBeAg) positive and 40 HBeAg negative; 193 hepatitis B surface antigen (HBsAg) positive and 11 HBsAg negative; 164 with detectable HBV deoxyribonucleic acid (DNA) and 40 with undetectable HBV DNA; 131 with HBV genotype B and 23 with HBV genotype C; and 27 without hepatic fibrosis and 97 with hepatic fibrosis. Serum levels of 25(OH)D, VDBP, liver function markers, and other clinical parameters were collected to analyze their association with vitamin D and VDBP. Mann-Whitney U test, Kruskal-Wallis H test, or t test was used to analyze serum 25(OH)D and VDBP levels in different groups. Spearman rank correlation test was utilized to analyze the correlation of 25(OH)D and VDBP with other markers. Statistically significant factors determined by univariate analysis were further analyzed by binary multivariate logistic regression analysis. P < 0.05 was considered statistically significant.RESULTSChildren with CHB had lower serum 25(OH)D (56.64 ± 17.89 nmoL/L) and VDBP [122.40 (70.74-262.84 μg/L)] levels than healthy controls had (P < 0.001). Serum 25(OH)D and VDBP levels were significantly different among the different grades of hepatic fibrosis (P < 0.05). VDBP levels in children with HBV genotype C, HBsAg, HBeAg, and detectable HBV DNA were significantly lower than those in children with HBV genotype B, no HBsAg, no HBeAg, and undetectable HBV DNA (P < 0.05). Serum 25(OH)D level was negatively correlated with age and serum total bilirubin level (r = -0.396 and -0.280, respectively, P < 0.001). Serum VDBP level was negatively correlated with HBV DNA (log10 IU/mL) (r = -0.272, P < 0.001). Serum 25(OH)D level was not correlated with VDBP level (P > 0.05). Univariate (P < 0.05) and multivariate logistic regression analysis showed that low level of 25(OH)D (odds ratio = 0.951, 95% confidence interval: 0.918-0.985) and high level of HBV DNA (odds ratio = 1.445, 95% confidence interval: 1.163-1.794) were independently correlated with hepatic fibrosis (P < 0.01).CONCLUSIONSerum levels of 25(OH)D and VDBP are decreased in children with CHB. Serum VDBP level is negatively correlated with HBV replication. Low level of 25(OH)D is independently associated with hepatic fibrosis in children with CHB. There is no significant association between serum levels of 25(OH)D and VDBP.

Associations between Vitamin D and Type 2 Diabetes Mellitus: The Role of Vitamin D Receptor and Binding Protein

Background: Type 2 diabetes mellitus (T2DM) is a chronic disease that is characterized by β-cell dysfunction and resistance for insulin. Vitamin D is necessary for insulin secretion so it is a crucial factor in the development of T2DM. This study was done to investigate the association between serum 25-hydroxy Vitamin D [25(OH)3D], VDR (Vitamin D receptor) and VDBP (Vitamin D binding protein) with type 2 diabetic patients compared to control subjects. Subjects and Methods: This study carried out 110 female patients who were previously diagnosed with type 2 diabetes and 110 age, sex and weight matched as controls. All participants were subjected to full history taking, clinical examination and assessment of fasting blood glucose, HbA1c , lipid profile, 25-hydroxy Vitamin D [25(OH)3D], VDR and VDBP. Results: Results showed that the level of 25(OH)3D was significantly lower in diabetic group compared to controls and was significantly negatively correlated with glycated hemoglobin, serum total cholesterol and low density lipoprotein cholesterol in type 2 DM. Decreasing Vitamin D level was significantly associated with decreasing VDR. No significant association was found between Vit D and VDBP levels. Conclusions: Vitamin D deficiency is frequent in diabetic patients and associated with poor control and outcome. This suggests a role of Vitamin D in the pathogenesis and control of T2DM. Serum VDBP in diabetes may be independent to the level of 25(OH)3D and needs further studies.