Serum Vitamin D-binding Protein Levels Research Articles

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 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 <2 days, 2–7 days, and >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.

Measuring Vitamin D Status in Chronic Inflammatory Disorders: How does Chronic Inflammation Affect the Reliability of Vitamin D Metabolites in Patients with IBD?

Evidence gained from recent studies has generated increasing interest in the role of vitamin D in extraskeletal functions such as inflammation and immunoregulation. Although vitamin D deficiency has been implicated in the pathophysiology of inflammatory diseases including inflammatory bowel disease (IBD), evidence as to whether vitamin D supplementation may cure or prevent chronic disease is inconsistent. Since 25OH-vitamin D (25OHD) has been suggested to be an acute-phase protein, its utility as a vitamin D status marker is therefore questionable. In this study, possible interactions of vitamin D and inflammation were studied in 188 patients with IBD, with high-sensitivity C-reactive protein (hsCRP) levels ≥ 5 mg/dL and/or fecal calprotectin ≥ 250 µg/g defined as biochemical evidence of inflammatory activity. Levels of 25OHD and vitamin D-binding protein (VDBP) were determined by ELISA, and 1,25-dihydroxyvitamin D (1,25OHD) and dihydroxycholecalciferol (24,25OHD) by LC-MS/MS. Free and bioavailable vitamin D levels were calculated with the validated formula of Bikle. Serum 1,25OH2D and vitamin D binding protein (VDBP) levels were shown to differ between the inflammatory and noninflammatory groups: patients with inflammatory disease activity had significantly higher serum concentrations of 1,25OH2D (35.0 (16.4–67.3) vs. 18.5 (1.2–51.0) pg/mL, p < 0.001) and VDBP (351.2 (252.2–530.6) vs. 330.8 (183.5–560.3) mg/dL, p < 0.05) than patients without active inflammation. Serum 24,25OH2D levels were negatively correlated with erythrocyte sedimentation rate (ESR) (−0.155, p = 0.049) while concentrations of serum 1,25OH2D correlated positively with hsCRP (0.157, p = 0.036). Correlations with serum VDBP levels were found for ESR (0.150, p = 0.049), transferrin (0.160, p = 0.037) and hsCRP (0.261, p < 0.001). Levels of serum free and bioavailable 25OHD showed a negative correlation with ESR (−0.165, p = 0.031, −0.205, p < 0.001, respectively) and hsCRP (−0.164, p = 0.032, −0.208, p < 0.001 respectively), and a moderate negative correlation with fecal calprotectin (−0.377, p = 0.028, −0.409, p < 0.016, respectively). Serum total 25OHD concentration was the only vitamin D parameter found to have no specific correlation with any of the inflammatory markers. According to these results, the traditional parameter, total 25OHD, still appears to be the best marker of vitamin D status in patients with inflammatory bowel disease regardless of the presence of inflammation.

Relative D3 vitamin deficiency and consequent cognitive impairment in an animal model of Alzheimer's disease: Potential involvement of collapsin response mediator protein-2

Alzheimer's disease (AD) starts with memory impairments that can be observed before the appearance of significant neuropathology; thus, identifying mechanisms to stop AD progression is an urgent priority. Epidemiological and clinical data show that the consequences of vitamin D deficiency are relevant to disease risk and can be observed in the progression of many diseases, especially AD, whereas higher serum levels of vitamin D are associated with better cognitive test performance. However, the potential therapeutic strategy and underlying mechanisms of vitamin D supplementation against AD still need to be further investigated. In the present study, we found that 3xTg-AD mice with vitamin D supplementation exhibited an increase in serum vitamin D concentrations and improved cognition. We measured serum vitamin D binding protein (VDBP) concentrations and found that serum VDBP levels were increased in 3xTg-AD mice compared to B6129S control mice, but there was no significant difference between control- and vitamin D-treated 3xTg-AD groups. The vitamin D-mediated memory improvement may be accompanied by the suppression of increased hippocampal collapsin response mediator protein-2 (CRMP2) phosphorylation, and the restoration of CRMP2 phosphorylation by okadaic acid (OA) could abolish the beneficial effects of vitamin D. In addition, we found that CRMP2 was associated with NR2B and PSD-95 in 3xTg-AD mice with vitamin D supplementation. This CRMP2-NR2B interaction could be disrupted by a TAT-CBD3 peptide or OA, leading to attenuated memory protection in vitamin D-treated 3xTg-AD mice. Therefore, CRMP2 may be involved in vitamin D-mediated memory improvement in AD.

Serum Proteomic Analysis Reveals Vitamin D-Binding Protein (VDBP) as a Potential Biomarker for Low Bone Mineral Density in Mexican Postmenopausal Women.

Osteoporosis is a skeletal disease mainly affecting women over 50 years old and it represents a serious public health problem because of the high socioeconomic burden. This disease is characterized by deterioration of bone microarchitecture, low bone mineral density (BMD), and increased risk of fragility fractures. This study aimed to identify serum useful proteins as biomarkers for the diagnosis and/or prognosis of osteoporosis and fracture risk. We collected 446 serum samples from postmenopausal women aged ≥45 years old. Based on the BMD measurement, we classified the participants into three groups: osteoporotic, osteopenic, and normal. In an initial discovery stage, we conducted a proteomic approach using two-dimensional differential gel electrophoresis (2D-DIGE). The peptides into the spots of interest were identified through matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF/TOF). Enzyme-linked immunosorbent assay (ELISA) was performed to validate the proteins of interest. We identified 27 spots of interest when comparing low BMD versus normal BMD postmenopausal women. Based on their relevance in bone metabolism, we analyzed three proteins: ceruloplasmin (CP), gelsolin (GSN), and vitamin D-binding protein (VDBP). Our results demonstrated that low serum VDBP levels correlate with low BMD (osteopenic and osteoporotic). Therefore, VDBP could be considered as a novel, potential, and non-invasive biomarker for the early detection of osteoporosis.

Cerebrospinal fluid vitamin D-binding protein as a new biomarker for the diagnosis of meningitis.

Meningitis is an inflammatory process involving meninges. It is difficult to diagnose because of the absence of a diagnostic biomarker. We first report here the possibility of cerebrospinal fluid (CSF) vitamin D-binding protein (VDBP) as a new biomarker for the diagnosis of meningitis. This prospective study enrolled a total of 102 subjects (58 patients with non-neurologic disease, 17 patients with meningitis, and 27 patients with other neurologic diseases) from 2017 to 2018. CSF and blood samples were collected in pairs. Total 25(OH)D in CSF and serum and VDBP levels in serum were measured. GC genotyping was also performed to determine polymorphisms of rs4588 and rs7041. CSF total 25(OH)D and VDBP levels were compared with serum total 25(OH)D and VDBP levels according to disease (meningitis vs. non-meningitis). Receiver operating characteristic (ROC) analysis for the diagnosis of meningitis using CSF VDBP level was performed. Mean CSF VDBP and serum VDBP levels of all patients were 1.48 ± 1.32 and 181.28 ± 56.90μg/mL, respectively. CSF VDBP level in the meningitis disease group (3.20 ± 1.49μg/mL) was significantly (P < 0.001) higher than that in other disease groups. According to ROC curve analysis, the appropriate cut-off value for CSF VDBP was 1.96μg/mL, showing sensitivity of 82.4% and specificity of 85.9%. AUC of CSF VDBP was 0.879 (95% CI: 0.789-0.962). CSF VDBP level showed very good diagnostic performance. It could be used as a potential biomarker for the diagnosis of meningitis.

Serum Vitamin D Binding Protein Level Associated with Metabolic Cardiovascular Risk Factors in Women with the Polycystic Ovary Syndrome.

The objective of the study was to measure the levels of 25-hydroxyvitamin D [25(OH)D] and vitamin D binding protein (VDBP) and assess their relationships with cardiovascular risk factors in women with the polycystic ovary syndrome (PCOS). A group of 267 women, aged 20-35 years (24.7 ± 4.9): 167 with PCOS and 100 healthy women were divided according to body mass index. Biochemical and hormonal parameters were measured. Free and bioavailable 25(OH)D were calculated using the mathematical equations. The percentage of body fat and visceral fat deposit were assessed by DXA. In the normal weight control group total, free, bioavailable 25(OH)D (p<0.001 for all) were significantly higher than in its overweight/obese counterpart, while VDBP levels were comparable. In PCOS women total 25(OH)D (p<0.001), and VDBP (p -0.006) were lower in the overweight/obese subgroups than in the normal weight ones. In both groups serum VDBP levels correlated negatively with serum insulin and positively with sex hormone binding globulin. In PCOS group, in contrast to control group, VDPB was negatively correlated with abdominal fat deposit, BMI, fasting glucose and positively with HDL. Despite lower total 25(OH)D in obese PCOS women, all women with PCOS (lean and obese) had comparable free and bioavailable 25(OH)D, which might be a result of concomitantly lowered serum VDBP levels in obese PCOS women. VDBP might play important role in the regulation of availability of active fractions of 25(OH)D in PCOS women. VDBP seems to be associated with cardiovascular risk factors such as BMI, waist circumference, visceral fat, and fasting serum insulin in women with PCOS.

Alteration of Serum 25(OH) Vitamin D, Vitamin D Binding Protein, and C-reactive Protein Levels in Acute Leukemia Patients.

Acute leukemia is a common hematologic malignancy with poorly differentiated leukocytes. Alteration of circulating vitamin D (VD) and its carrier vitamin D binding protein (VDBP) have been reported in certain types of cancers and may play a role in the course of the disease. Understanding of the status of serum VD and VDBP, as well as the acute phase protein C-reactive protein (CRP) levels in pre- and post-treatment of acute leukemia patients, may be helpful in the management of acute leukemia. Enzyme linked immunosorbent assay (ELISA), chemiluminescence immunoassay, and immunofluorescent assay were used to analyze the 25(OH) vitamin D (25(OH)D), VDBP, and CRP in the serum of a cohort of leukemia patients. Serum 25(OH)D levels in patients (pre- and post-treatment) were significantly lower than in control subjects. There was no significant difference in 25(OH)D levels between pre- and post-treatment. Serum VDBP level was raised in both pre- and post-treatment of acute leukemia patients, with that of pre-treatment being higher. The average serum VDBP was reduced in post-treatment; however, no significant difference was found. Elevated serum CRP levels in both pre- and post-treatment patient groups have been observed but were reduced significantly after treatment. Results also revealed that serum VDBP levels in acute myeloid leukemia patients were significantly higher than in acute lymphoid leukemia patients, while 25(OH)D levels in acute myeloid leukemia were significantly lower than in acute lymphoid leukemia. No significant difference between the serum CRP levels of acute myeloid leukemia and acute lymphoid leukemia was observed. Serum 25(OH)D, VDBP, and CRP may be used together and could be potential indicators of the disease course of acute leukemia and assist in its management which merits further investigation.

Independent assortment of GC gene polymorphism (rs2282679) and 25-hydroxyvitamin D levels in coronary artery disease.

Coronary artery disease (CAD) remains a major public health burden. Emerging research has suggested an association between vitamin D insufficiency and CAD. Vitamin D binding protein (VDBP) is the primary vitamin D carrier and many of its genetic polymorphisms are able to induce the expression of proteins with different affinities for the vitamin, which in turn might affect its serum levels and CAD incidence. One hundred and twelve male patients, aged between 35 and 50 years, with verified CAD and 109 age- and sex-matched controls were recruited. Genotyping was performed by the TaqMan allelic discrimination assay and plasma 25(OH)D levels were assessed by HPLC-UV. Serum parathyroid hormone (s-PTH) and VDBP levels were measured using ELISA. s-25(OH)D levels in CAD patients were significantly lower than in the controls, whereas s-PTH levels were significantly higher in the CAD patients than in the controls. There was no significant difference in the distribution of GC genotypes among both groups. s-25(OH)D showed a weak inverse correlation with s-PTH levels. Serum levels of vitamin D and PTH are highly correlated with CAD incidence. However, the s-VDBP level is associated neither with disease outcome nor with vitamin D status. The GC gene variant has no effect on 25(OH)D levels.

Vitamin D-binding protein and free vitamin D concentrations in acromegaly.

Free 25-hydroxyvitamin D [25(OH)D] is suggested to be important in the determination of vitamin D deficiency, since vitamin D-binding protein (VDBP) may affect total 25(OH)D levels. There are no data about free 25(OH)D concentrations in acromegaly. We aimed to investigate serum VDBP and total and free 25(OH)D levels in patients with acromegaly in comparison with control subjects. We recruited 54 patients with acromegaly and 32 control subjects who were similar according to age, gender, and body mass index. Serum VDBP levels were found to be increased in patients with acromegaly compared to control subjects [90.35 (72.45-111.10) vs. 69.52 (63.89-80.13) mg/l, p = 0.001]. There was statistically no significant difference in serum total 25(OH)D levels between the patients with acromegaly and control subjects [18.63 (13.35-27.73) vs. 22.51 (19.20-28.96) ng/ml, p = 0.05]. Free 25(OH)D levels were significantly decreased in patients with acromegaly compared to control subjects [14.55 (10.45-21.45) vs. 17.75 (15.30-23.75) pg/ml, p = 0.03]. Free 25(OH)D levels correlated positively with total 25(OH)D (p = 0.0001) and HDL cholesterol (p = 0.04) and negatively with fasting blood glucose (p = 0.04). Our findings indicate that VDBP is increased and free 25(OH)D is decreased in acromegaly, while there is no significant alteration in total 25(OH)D.

Decreased serum vitamin D levels are associated with diabetic peripheral neuropathy in a rural area of Turkey.

Data examining the association between vitamin D and diabetic peripheral neuropathy are limited. This study investigated the serum levels of vitamin D, vitamin D-binding protein (VDBP), and vitamin D receptor (VDR) in diabetics in the Yozgat region of Turkey, and assessed their relationships with diabetic peripheral neuropathy. 69 diabetic patients and 49 age- and sex-matched control subjects were enrolled in this clinical prospective study. All the diabetics underwent conventional sensory and motor nerve conduction studies, and diabetic peripheral neuropathy was confirmed or ruled out according to the electromyography findings and Douleur Neuropathique 4 questions. Serum vitamin D, VDBP and VDR levels were measured using commercial enzyme-linked immunosorbent assay kits. The serum vitamin D levels (p = 0.001) were significantly lower, while the VDR levels (p = 0.003) were higher, in diabetics than in controls. The serum VDBP levels were similar in both groups (p > 0.05). The serum vitamin D levels were significantly lower in diabetics with diabetic peripheral neuropathy than in those without (p = 0.032), whereas the serum VDBP and VDR levels were similar in these two groups (p > 0.05). The lower serum vitamin D levels in diabetics, especially in those with peripheral neuropathy, may suggest a neurotrophic effect of vitamin D.

Serum levels of vitamin D, vitamin D-binding protein and vitamin D receptor in migraine patients from central Anatolia region.

Inflammation is proposed to be involved in the pathogenesis of both vitamin D deficiency and migraine. However, the data examining the relation of vitamin D with migraine are limited. We aimed to investigate the serum levels of vitamin D, vitamin D-binding protein (VDBP) and vitamin D receptor (VDR) in combination, in migraine patients from central Anatolia region. Fifty-two newly diagnosed migraine patients and age- and sex-matched 49 control subjects were enrolled in this cross-sectional prospective study. Migraine diagnosis was settled according to the International Classification of Headache Disorders-II diagnostic criteria. Serum samples were analysed for the measurement of vitamin D, VDBP and VDR levels by using commercial enzyme-linked immuno sorbent assay kits. Serum vitamin D and VDR levels were found to be significantly lower in migraine patients than in controls (p=0.012 and p=0.038, respectively); whereas serum VDBP levels were similar between the groups (p>0.05). There was no correlation between serum vitamin D, VDBP and VDR levels and headache characteristics including aura, attack severity, frequency and duration, and disease duration (p>0.05). In terms of headache characteristics, no significant difference between migraineurs with vitamin D values <25 and ≥25ng/ml was observed (p>0.05). The present findings may suggest that decreased serum vitamin D levels were associated with migraine.

Reduced Serum Vitamin D–Binding Protein Levels Are Associated With Type 1 Diabetes

OBJECTIVEPrevious studies have noted a specific association between type 1 diabetes and insufficient levels of vitamin D, as well as polymorphisms within genes related to vitamin D pathways. Here, we examined whether serum levels or genotypes of the vitamin D–binding protein (VDBP), a molecule key to the biologic actions of vitamin D, specifically associate with the disorder.RESEARCH DESIGN AND METHODSA retrospective, cross-sectional analysis of VDBP levels used samples from 472 individuals of similar age and sex distribution, including 153 control subjects, 203 patients with type 1 diabetes, and 116 first-degree relatives of type 1 diabetic patients. Single nucleotide polymorphism (SNP) typing for VDBP polymorphisms (SNP rs4588 and rs7041) was performed on this cohort to determine potential genetic correlations. In addition, SNP analysis of a second sample set of banked DNA samples from 1,502 type 1 diabetic patients and 1,880 control subjects also was used to determine genotype frequencies.RESULTSSerum VDBP levels were highest in healthy control subjects (median 423.5 µg/mL [range 193.5–4,345.0; interquartile range 354.1–]586), intermediate in first-degree relatives (402.9 µg/mL [204.7–4,850.0; 329.6–492.4]), and lowest in type 1 diabetic patients (385.3 µg/mL [99.3–1,305.0; 328.3–473.0]; P = 0.003 vs. control subjects). VDBP levels did not associate with serum vitamin D levels, age, or disease duration. However, VDBP levels were, overall, lower in male subjects (374.7 µg/mL [188.9–1,602.0; 326.9–449.9]) than female subjects (433.4 µg/mL [99.3–4,850.0; 359.4–567.8]; P < 0.0001). It is noteworthy that no differences in genotype frequencies of the VDBP polymorphisms were associated with serum VDBP levels or between type 1 diabetic patients and control subjects.CONCLUSIONSSerum VDBP levels are decreased in those with type 1 diabetes. These studies suggest that multiple components in the metabolic pathway of vitamin D may be altered in type 1 diabetes and, collectively, have the potential to influence disease pathogenesis.