Search Results (10)

Background: This study explored the association between ApaI–TaqI Single Nucleotide Polymorphisms (SNPs) in a Vitamin D receptor (VDR) and the risk of Gestational Diabetes Mellitus (GDM) in Saudi women, along with the serum levels of vitamin D. Methods: Ninety women with GDM and 90 non-GDM women were enrolled, based on the inclusion and exclusion criteria for pregnant women enrolled in a single-center study. Blood samples were retrieved from 180 pregnant women using ethylenediaminetetraacetic acid (EDTA) tubes. Serum samples were used to measure the vitamin D, 25-hydroxyvitamin D (25(OH)D or calcidiol), and lipid profiles. Blood was used to measure the hemoglobin A1c levels and to isolate the DNA. The polymerase chain reaction (PCR) was performed for the ApaI (rs79785232), BsmI (rs1544410), FokI (rs2228570), and TaqI (rs731236) SNPs in the VDR gene using restriction fragment length polymorphism analysis. Validation was performed using Sanger sequencing. Statistical analyses were performed between the patients with and without GDM using various statistical software packages. Results: The Hardy–Weinberg equilibrium analysis was statistically significant (p > 0.05). The ApaI, BsmI, and TaqI SNPs were associated with alleles, genotypes, and different genetic models (p < 0.05). Vitamin D levels were associated with deficient levels (p = 0.0002), as well as with a normal and overweight body mass index (p = 0.0004). When vitamin D levels were measured with GDM covariates, the fasting plasma glucose (FPG) (p = 0.0001), postprandial blood glucose (PPBG) (p < 0.0001), oral glucose tolerance test (OGTT)-1 h (p = 0.005), high-density lipoprotein (p = 0.022), and low-density lipoprotein cholesterol (LDLc) (p = 0.001) levels were significantly different. When similar vitamin D levels were measured for each genotype, we confirmed that the ApaI SNP was associated with sufficient levels (p < 0.0001), whereas the BsmI, FokI, and TaqI (p < 0.05) were associated with insufficient levels. The logistic regression model confirmed that the first hour of the OGTT (p = 0.005) was strongly associated with GDM, whereas the analysis of variance confirmed that FPG and PPBG (p < 0.05) were strongly associated with all the SNPs evaluated in the VDR gene. Additionally, the second hour of the OGTT (p = 0.048) and LDLc (p = 0.049) were associated with the ApaI and FokI SNP. Moreover, the first hour OGTT (p = 0.045) and lipid profile parameters (p < 0.05) were associated. Haplotype analysis revealed positive associations among the examined SNPs, which seemed compatible with the hypothesis that variants and combinations of multiple SNP genotypes enhance the risk of GDM in women. Haplotype analysis revealed that different combinations of alleles, such as AGCC, CATT, CGTC, AGTC, and CATT (p < 0.05), were strongly associated. The linkage disequilibrium (LD) analysis showed a strong association with all combinations (p < 0.05). Among the gene–gene interactions, all possible combinations showed a positive association (p < 0.05). Conclusions: Low vitamin D levels were observed in women with GDM. The ApaI, BsmI, and TaqI SNPs were associated with genotype and allele frequencies (p < 0.05). Vitamin D and the SNPs in the VDR gene were associated, according to the ANOVA, logistic regression, haplotype analysis, LD analysis, and the generalized multifactor dimensionality reduction model (p < 0.05). Full article

Vitamin D is necessary for the normal functioning of many organs, including the thyroid gland. It is, therefore, not surprising that vitamin D deficiency is considered a risk factor for the development of many thyroid disorders, including autoimmune thyroid diseases and thyroid cancer. However, the interaction between vitamin D and thyroid function is still not fully understood. This review discusses studies involving human subjects that (1) compared vitamin D status (primarily determined by serum calcidiol (25-hydroxyvitamin D [25(OH)D]) levels) with thyroid function assessed by thyroid stimulating hormone (TSH), thyroid hormones, and anti-thyroid antibody levels; and (2) evaluated the effect of vitamin D supplementation on thyroid function. Due to the many inconsistencies in the results between the studies, it is still difficult to draw a definite conclusion on how vitamin D status affects thyroid function. Studies in healthy participants observed either a negative correlation or no association between TSH and 25(OH)D levels, while the results for thyroid hormones showed high variability. Many studies have observed a negative association between anti-thyroid antibodies and 25(OH)D levels, but equally many studies have failed to observe such an association. Regarding the studies that examined the effect of vitamin D supplementation on thyroid function, almost all observed a decrease in anti-thyroid antibody levels after vitamin D supplementation. Factors that could contribute to the high variability between the studies are the use of different assays for the measurement of serum 25(OH)D levels and the confounding effects of sex, age, body-mass index, dietary habits, smoking, and the time of year when the samples were collected. In conclusion, additional studies with larger numbers of participants are needed to fully understand the effect of vitamin D on thyroid function. Full article

Background: The aim of the present review was to summarize the current evidence about the impact of vitamin D deficiency on pathology and clinical manifestations of Sjögren’s disease (SD). Methods: Databases PubMed, Web of Science, Scopus, and Cochrane library were searched for studies assessing the levels of vitamin D in SD patients using the following keywords: (vitamin D OR calciferol OR cholecalciferol OR 25-hydroxyvitamin D OR 25-hydroxycholecalciferol OR calcidiol OR calcitriol OR 1,25-dihydroxycholecalciferol) AND (Sjögren’s Syndrome OR Sjögren’s disease) accessed on 20 September 2022. Out of 248 retrieved studies, following the systematic review methodology and defined inclusion and exclusion criteria, 9 clinical studies were eligible to be included in the present review: 4 of them case-control, 4 cross-sectional, and 1 cohort study. Results: Nine studies totaling 670 SD patients and 857 healthy controls were eligible for meta-analysis with moderate to high methodological quality as determined by the Newcastle–Ottawa Quality Scale (NOS). According to the obtained results, a high prevalence of hypovitaminosis D was observed in SD patients when compared to healthy controls (95% CI −10.43, −2.39; p < 0.01). Conclusion: Available evidence points to lower levels of vitamin D in patients with SD in comparison to healthy controls. However, further studies are necessary to understand the underlying mechanisms associated with the role of vitamin D in the development and disease severity of SD. Full article

Background: Vitamin D₃ complexed to deglycosylated vitamin D binding protein (VitD-dgVDBP) is a water-soluble vitamin D dimeric compound (VitD-dgVDBP). It is not clear how VitD-dgVDBP affects circulating monocytes, macrophages, other immune cell systems, including phagocytosis and apoptosis, and the generation of reactive oxygen species (ROS) compared to dgVDBP. Methods: Flow cytometry was used to measure superoxide anion radical (O₂^*−) levels and macrophage activity in the presence of VitD-dgVDBP or dgVDBP. VitD-dgVDBP was incubated with normal human lymphocytes (nPBMCs), and several clusters of determination (CDs) were estimated. dgVDBP and VitD-dgVDBP apoptosis was estimated on malignant prostatic cells. Results: The macrophage activity was 2.8-fold higher using VitD-dgVDBP (19.8·10⁶ counts) compared to dgVDBP (7.0·10⁶ counts), but O₂^*− production was 1.8-fold lower in favor of VitD-dgVDBP (355·10³ counts) compared to dgVDBP (630·10⁶ counts). The calculated ratio of the radical/macrophage activity was 5-fold lower compared to that of dgVDBP. Only VitD-dgVDBP activated caspase-3 (8%), caspase-9 (13%), and cytochrome-C (11%) on prostatic cancer cells. PE-Cy7-labeled VitD-dgVDBP was found to bind to cytotoxic suppressor cells, monocytes/macrophages, dendritic and natural killer cells (CD8+), and helper cells (CD4+). After 12 h of co-incubation of nPBMCs with VitD-dgVDBP, significant activation and expression were measured for CD16++/CD16 (0.6 ± 0.1% vs. 0.4 ± 0.1%, p < 0.05), CD45k⁺ (96.0 ± 6.0% vs. 84.7 ± 9.5%, p < 0.05), CD85k⁺ (24.3 ± 13.2% vs. 3.8 ± 3.2%, p < 0.05), and CD85k⁺/CD123⁺ (46.8 ± 8.1% vs. 3.5 ± 3.7%, p < 0.001) compared to the control experiment. No significant difference was found using CD3+, CD4+, CD8+, CD4/CD8, CD4/CD8, CD16+, CD16++, CD14+, or CD123+. A significant decline in CD14+/CD16+ was obtained in the presence of VitD-dgVDBP (0.7 ± 0.2% vs. 3.1 ± 1.7%; p < 0.01). Conclusion: The newly developed water-soluble VitD₃ form VitD-dgVDBP affected cytotoxic suppressor cells by activating the low radical-dependent CD16 pathway and seemed to induce apoptosis in malignant prostatic cells. Full article

Background. Mineral metabolism (MM) system and N-terminal pro-brain natriuretic peptide (NT-ProBNP) have been shown to add prognostic value in patients with stable coronary artery disease (SCAD). However, the influence of NT-ProBNP on the prognostic role of MM in patients with SCAD has not been shown yet. The objective of this study is to assess the influence of NT-ProBNP on the prognostic role of MM markers in patients with SCAD. Methods: We analyzed the prognostic value of MM markers (parathormone (PTH), klotho, phosphate, calcidiol (25-hydroxyvitamin D₃), and fibroblast growth factor-23) in 964 patients with SCAD and NT-ProBNP > 125 pg/mL vs. patient with NT-ProBNP ≤ 125 pg/mL included in five hospitals in Spain. The main outcome was the combination of death, heart failure, and ischemic events (any acute coronary syndrome, ischemic stroke, or transient ischemic attack). Results: A total of 622 patients had NT-proBNP > 125 pg/mL and 342 patients had NT-ProBNP ≤ 125 pg/mL. The median follow-up was 5.1 years. In the group of NT-proBNP > 125 pg/mL, the patients were older, and there were more females and smokers than in the group of patients with normal NT-proBNP. Additionally, the proportion of patients with hypertension, atrial fibrillation, ejection fraction < 40%, cerebrovascular attack, or prior coronary artery bypass graft was higher in the high NT-proBNP group. In the high NT-proBNP patients, the predictors of poor prognosis were PTH (HR = 1.06 (1.01–1.10), p < 0.001) and NT-proBNP (HR = 1.02 (1.01–1.03), p = 0.011), along with age (HR = 1.039 (1.02–1.06), p < 0.001), prior coronary artery bypass graft (HR = 1.624 (1.02–2.59), p = 0.041), treatment with statins (HR = 0.32 (0.19–0.53), p < 0.001), insulin (HR = 2.49 (1.59–4.09), p < 0.001), angiotensin receptor blockers (HR = 1.73 (1.16–2.56), p = 0.007), nitrates (HR = 1.65 (1.10–2.45), p = 0.014), and proton pump inhibitors (HR = 2.75 (1.74–4.36), p < 0.001). In the NT-proBNP ≤ 125 pg/mL subgroup, poor prognosis predictors were plasma levels of non-high-density lipoprotein (non-HDL) cholesterol (HR = 1.01 (1.00–1.02), p = 0.014) and calcidiol (HR = 0.96 (0.92–0.99), p = 0.045), as well as treatment with verapamil (HR = 11.28 (2.54–50.00), p = 0.001), and dihydropyridines (HR = 3.16 (1.63–6.13), p = 0.001). Conclusion: In patients with SCAD and NT-ProBNP > 125 pg/mL, PTH and NT-ProBNP, which are markers related to ventricular damage, are predictors of poor outcome. In the subgroup of patients with NT-ProBNP ≤ 125 pgm/L, calcidiol and non-HDL cholesterol, which are more related to vascular damage, are the independent predictors of poor outcome. Then, in patients with SCAD, baseline NT-ProBNP may influence the type of biomarker that is effective in risk prediction. Full article

Vitamin D deficiency has been linked to numerous health problems, including those resulting from disturbed calcium-phosphorus homeostasis, and neuropsychiatric and autoimmune disorders. Nearly one-third of the global population has suboptimal levels of vitamin D, according to epidemiological data. Vitamin D status is usually determined by measuring serum 25(OH)D, but, for decades, serum 25(OH)D measurement has been hampered by a lack of standardization. There have been many recent initiatives to develop reference substances and methods for measuring vitamin D and its metabolites, and re-evaluating the optimal values. It was also suggested that alternative biological samples could also be used, such as hair, since it has been established that lipophilic substances, such as corticosteroids, can also be found in hair. The purpose of this study was to determine the correlation between 25(OH)D3 concentrations in serum and hair, and other demographic features in 26 healthy Caucasian young adult volunteers. The determination of 25(OH)D3 and cholecalciferol was carried out using liquid chromatography coupled with mass spectrometry (LC-MS) from blood and hair samples taken at two timepoints separated by nine weeks. In the hair samples of 18 out of 26 subjects, 25(OH)D was detected at a mean (±SEM) concentration of 17.07 ± 5.375 pg/mg at the first sampling time, and 58.90 ± 25.97 pg/mg at the second sampling time. A multiple linear regression analysis revealed no effects of gender, body mass index, supplementation, or sun exposure on hair 25(OH)D3 concentrations, but supplementation and sun exposure significantly increased serum 25(OH)D3 concentrations. In addition, serum and hair 25(OH)D3 concentrations did not correlate; however, there was a strong correlation between the two sampling times for serum 25(OH)D3 concentrations. In conclusion, this study confirmed that 25(OH)D3 could be detected in human hair, but its use as a biomarker warrants further investigations since no link was found between serum 25(OH)D3 concentrations, supplementation, sun exposure, and hair 25(OH)D3 concentrations levels. Full article

The prevalence, determinants, and clinical significance of vitamin D deficiency in the population are debated. The population-based study investigated the cross-sectional associations of several variables with serum 25-hydroxyvitamin D (calcidiol) measured using standardized calibrators. The study cohort consisted of 979 persons of the Moli-sani study, both sexes, ages ≥35 years. The correlates in the analyses were sex, age, education, local solar irradiance in the month preceding the visit, physical activity, anthropometry, diabetes, kidney function, albuminuria, blood pressure, serum cholesterol, smoking, alcohol intake, calorie intake, dietary vitamin D intake, and vitamin D supplement. The serum calcidiol was log transformed for linear regression because it was positively skewed (skewness = 1.16). The prevalence of calcidiol deficiency defined as serum calcidiol ≤12 ng/mL was 24.5%. In multi-variable regression, older age, lower solar irradiance, lower leisure physical activity, higher waist/hip ratio, higher systolic pressure, higher serum cholesterol, smoking, lower alcohol intake, and no vitamin D supplement were independent correlates of lower serum calcidiol (95% confidence interval of standardized regression coefficient ≠ 0) and of calcidiol deficiency (95% confidence interval of odds ratio > 1). The data indicate that low serum calcidiol in the population could reflect not only sun exposure, age, and vitamin D supplementation but also leisure physical activity, abdominal obesity, systolic hypertension, hypercholesterolemia, smoking, and alcohol intake. Full article

Recent evidence has revealed anti-inflammatory properties of vitamin D as well as extra-skeletal activity. In this context, vitamin D seems to be involved in infections, autoimmune diseases, cardiometabolic diseases, and cancer development. In recent years, the relationship between vitamin D and insulin resistance has been a topic of growing interest. Low 25-hydroxyvitamin D (25(OH)D) levels appear to be associated with most of the insulin resistance disorders described to date. In fact, vitamin D deficiency may be one of the factors accelerating the development of insulin resistance. Vitamin D deficiency is a common problem in the population and may be associated with the pathogenesis of diseases related to insulin resistance, such as obesity, diabetes, metabolic syndrome (MS) and polycystic ovary syndrome (PCOS). An important question is the identification of 25(OH)D levels capable of generating an effect on insulin resistance, glucose metabolism and to decrease the risk of developing insulin resistance related disorders. The benefits of 25(OH)D supplementation/repletion on bone health are well known, and although there is a biological plausibility linking the status of vitamin D and insulin resistance supported by basic and clinical research findings, well-designed randomized clinical trials as well as basic research are necessary to know the molecular pathways involved in this association. Full article

Opinions are conflicting about the epidemiology of vitamin D deficiency. This population-based study investigated cross-sectionally the associations of 25-hydroxyvitamin D (calcidiol) and 1,25-dihydroxyvitamin D (calcitriol) with indices of mineral homeostasis. Study cohort consisted of 979 persons of the Moli-Sani study, both sexes, ages ≥35 years. Data collection included serum calcidiol by different assays, serum calcitriol, serum parathyroid hormone, serum and urine calcium, and phosphorus. Prevalence of mild-to-moderate calcidiol deficiency (10–19 ng/mL) was 36.4% and did not associate with hypocalcemia or hyperparathyroidism. Prevalence of severe calcidiol deficiency (<10 ng/mL) was 16.8% and associated with hyperparathyroidism only (odds ratio = 8.81, 95% confidence interval = 2.4/32.9). Prevalence of calcitriol deficiency (<18 pg/mL) was 3.1% and associated with hypocalcemia (29.1, 7.4/114.5) but not hyperparathyroidism. In ANOVA along concentration strata, lower calcidiol associated with higher parathyroid hormone only (p < 0.001). Lower calcitriol associated with lower serum and urine calcium (p < 0.001) but not with parathyroid hormone. Calcidiol findings were consistent with different calcidiol assays. In the population, mild-to-moderate calcidiol deficiency did not associate with abnormal mineral homeostasis. Severe calcidiol deficiency and calcitriol deficiency associated with different disorders: lower calcidiol associated with hyperparathyroidism whereas lower calcitriol associated with hypocalcemia and low urine calcium. Full article

Low 25-hydroxyvitamin D (25(OH)D) and elevated C-reactive protein (CRP) concentrations are independently associated with adverse health outcomes, including cardiovascular disease (CVD). Although an inverse association between these factors has been described, the underlying mechanisms remain unknown. We postulate that environment–gene interactions, through which 25(OH)D interacts with single nucleotide polymorphisms (SNPs) within the CRP gene, modulate CRP; that certain CRP genotypes predispose individuals to a co-phenotype of low 25(OH)D and elevated CRP concentrations; and that this co-phenotype is associated with higher CVD risk. Twelve CRP SNPs were genotyped, and both 25(OH)D and CRP were quantified, in 505 black South African women. Alarmingly, 66% and 60% of the women presented with deficient/insufficient 25(OH)D and elevated CRP concentrations, respectively. CRP concentrations were higher in individuals with lower 25(OH)D concentrations. However, no 25(OH)D–CRP genotype interactions were evident. Several genotypes were associated with an altered risk of presenting with the co-phenotype, indicating a genetic predisposition. Women presenting with this co-phenotype had higher blood pressure and increased anthropometric measures, which may predispose them to develop CVD. We recommend increasing vitamin D fortification and supplementation efforts to reduce inflammation among black women with vitamin D deficiency, thereby possibly curbing diseases contingent on the co-phenotype described here. Full article