Serum parathyroid hormone is related to genetic variation in vitamin D binding protein with respect to total, free, and bioavailable 25-hydroxyvitamin D in middle-aged Caucasians – a cross-sectional study

Saarnio, Elisa; Pekkinen, Minna; Itkonen, Suvi T.; Kemi, Virpi; Karp, Heini; Kärkkäinen, Merja; Mäkitie, Outimaija Sinikka; Lamberg‐Allardt, Christel

doi:10.1186/s40795-016-0085-3

Cited by 11 publications

(15 citation statements)

References 24 publications

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“…Also the DBP genotype can influence the measured DBP concentrations as well as on DBP’s ability to bind 25(OH)D. In our previous study of the same study population, we found genetic differences in DBP, 25(OH)D Free , and 25(OH)D Bio concentrations [ 45 ]. In addition, Almesri et al .…”

Section: Discussionmentioning

confidence: 99%

Low free 25-hydroxyvitamin D and high vitamin D binding protein and parathyroid hormone in obese Caucasians. A complex association with bone?

et al. 2018

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BackgroundStudies have shown altered vitamin D metabolism in obesity. We assessed differences between obese and normal-weight subjects in total, free, and bioavailable 25-hydroxyvitamin D (25(OH)D, 25(OH)DFree, and 25(OH)DBio, respectively), vitamin D binding protein (DBP), parathyroid hormone (PTH) and bone traits.Methods595 37-47-year-old healthy Finnish men and women stratified by BMI were examined in this cross-sectional study. Background characteristic and intakes of vitamin D and calcium were collected. The concentrations of 25(OH)D, PTH, DBP, albumin and bone turnover markers were determined from blood. 25(OH)DFree and 25(OH)DBio were calculated. pQCT was performed at radius and tibia.ResultsMean±SE (ANCOVA) 25(OH)DFree (10.8±0.6 vs 12.9±0.4 nmol/L; P = 0.008) and 25(OH)DBio (4.1±0.3 vs 5.1±0.1 nmol/L; P = 0.003) were lower in obese than in normal-weight women. In men, 25(OH)D (48.0±2.4 vs 56.4±2.0 nmol/L, P = 0.003), 25(OH)DFree (10.3±0.7 vs 12.5±0.6 pmol/L; P = 0.044) and 25(OH)DBio (4.2±0.3 vs 5.1±0.2 nmol/L; P = 0.032) were lower in obese. Similarly in all subjects, 25(OH)D, 25(OH)DFree and 25(OH)DBio were lower in obese (P<0.001). DBP (399±12 vs 356±7mg/L, P = 0.008) and PTH (62.2±3.0 vs 53.3±1.9 ng/L; P = 0.045) were higher in obese than in normal-weight women. In all subjects, PTH and DBP were higher in obese (P = 0.047and P = 0.004, respectively). In obese women, 25(OH)D was negatively associated with distal radius trabecular density (R2 = 0.089, P = 0.009) and tibial shaft cortical strength index (CSI) (R2 = 0.146, P = 0.004). 25(OH)DFree was negatively associated with distal radius CSI (R2 = 0.070, P = 0.049), radial shaft cortical density (CorD) (R2 = 0.050, P = 0.045), and tibial shaft CSI (R2 = 0.113, P = 0.012). 25(OH)DBio was negatively associated with distal radius CSI (R2 = 0.072, P = 0.045), radial shaft CorD (R2 = 0.059, P = 0.032), and tibial shaft CSI (R2 = 0.093, P = 0.024).ConclusionsThe associations between BMI and 25(OH)D, 25(OH)DFree, and 25(OH)DBio, DBP, and PTH suggest that obese subjects may differ from normal-weight subjects in vitamin D metabolism. BMI associated positively with trabecular bone traits and CSI in our study, and slightly negatively with cortical bone traits. Surprisingly, there was a negative association of free and bioavailable 25(OH)D and some of the bone traits in obese women.

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Section: Discussionmentioning

confidence: 99%

Low free 25-hydroxyvitamin D and high vitamin D binding protein and parathyroid hormone in obese Caucasians. A complex association with bone?

et al. 2018

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“…The studied SNPs were previously selected from the HapMap project database (33), preferring functional polymorphisms with high heterozygosity levels and previously shown associations with 25OHD concentrations (34). Genotyping of SNPs rs2282679, rs4588, rs7041 and rs1155563 was performed using TaqMan Assays (Thermo-Fisher, Waltham, MA, USA) (Taqman SNP Assay ID: C__26407519_10, C__8278879_10, C__3133594_30 and C__8278782_20 respectively) and the qPCR Bio-Rad CFX384 C1000 Touchä Real-Time PCR Detection System (Bio-Rad, Hercules, CA, USA) or the qPCR ABI Prism 7900HT system (Applied Biosystems, Foster City, CA, USA), according to manufacturers' instructions.…”

Section: B Genotype Analysismentioning

confidence: 99%

Genetic Variation of the Vitamin D Binding Protein Affects Vitamin D Status and Response to Supplementation in Infants

Enlund-Cerullo

Koljonen

Holmlund-Suila

et al. 2019

The Journal of Clinical Endocrinology &Amp; Metabolism

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Context Single nucleotide polymorphisms (SNPs) of the vitamin D binding protein encoding the GC (group component) gene affect 25-hydroxyvitamin D (25OHD) concentrations, but their influence on vitamin D status and response to vitamin D supplementation in infants is unknown. Objective To study GC genotype–related differences in 25OHD concentrations and the response to supplementation during a vitamin D intervention study in infants. Design In this randomized controlled trial, healthy term infants received vitamin D3 (10 or 30 μg/d) from 2 weeks to 24 months of age. GC SNPs rs2282679, rs4588, rs7041, and rs1155563 were genotyped. rs4588/7041 diplotype and haplotypes of rs2282679, rs4588, and rs7041 (Haplo3SNP) and of all four SNPs (Haplo4SNP) were determined. Main Outcome Measures 25OHD measured in cord blood at birth and at 12 and 24 months during intervention. Results A total of 913 infants were included. Minor allele homozygosity of all studied GC SNPs, their combined haplotypes, and rs4588/rs7041 diplotype 2/2 were associated with lower 25OHD concentrations at all time points in one or both intervention groups [analysis of covariance (ANCOVA) P < 0.043], with the exception of rs7041, which did not affect 25OHD at birth. In the high-dose supplementation group receiving 30 μg/d vitamin D3, but not in those receiving 10 µg/d, genotype of rs2282679, rs4588, and rs7041; diplotype; and Haplo3SNP significantly affected intervention response (repeated measurement ANCOVA Pinteraction < 0.019). Minor allele homozygotes had lower 25OHD concentrations and smaller increases in 25OHD throughout the intervention. Conclusions In infants, vitamin D binding protein genotype affects 25OHD concentration and efficiency of high-dose vitamin D3 supplementation.

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“…Bioavailable and free 25(OH)D concentrations were calculated based on the levels of total 25(OH)D, VDBP, albumin, and their affinity constants derived from the VDBP genotypes [13,14]. We used the following equation for calculating free 25(OH)D concentrations:…”

Section: Vdbp Total Non-bioavailable Bioavailable and Free 25(oh)d Measurementsmentioning

confidence: 99%

Distribution and Determinants of Vitamin D-Binding Protein, Total, “Non-Bioavailable”, Bioavailable, and Free 25-Hydroxyvitamin D Concentrations among Older Adults

et al. 2021

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Background: serum 25-hydroxyvitamin D (25(OH)D) (“total 25 OH(D)”) is the most commonly used indicator of vitamin D status. However, 25(OH)D is mostly bound to the vitamin D binding protein (VDBP) or albumin in blood, and it has been suggested that the remaining bioavailable or free 25(OH)D may be more relevant for vitamin D associated health outcomes. We aimed to explore distributions and determinants of VDBP, total, bioavailable, complementary “non-bioavailable”, and free 25(OH)D in a large cohort of older adults in Germany. Methods: total 25(OH)D, VDBP, and albumin concentrations were measured in blood samples of 5899 men and women aged 50–75 years and used to calculate bioavailable (and complementary “non-bioavailable”) and free 25(OH)D concentrations. Linear regression models were used to evaluate associations of potential determinants of the various vitamin D biomarkers. Results: mean concentrations of VDBP, total, non-bioavailable, bioavailable, and free 25(OH)D were 323.6 µg/mL, 49.8 nmol/L, 43.4 nmol/L, 2.5 ng/mL, and 5.7 pg/mL, respectively. Seasonal variations were observed for all markers, with peak values in spring for VDBP and in summer for total, non-bioavailable, bioavailable, and free 25(OH)D. Consistent inverse associations were seen with age and body mass index for all markers, but divergent associations were seen with C-reactive protein. Strong variations by VDBP genotypes were seen for bioavailable and free 25(OH)D, and, in opposite direction for non-bioavailable 25(OH)D. Conclusion: commonalities and differences in determinants of various markers of vitamin D status were observed, which may help to enable a better understanding of their potential role for various vitamin D related health outcomes.

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Serum parathyroid hormone is related to genetic variation in vitamin D binding protein with respect to total, free, and bioavailable 25-hydroxyvitamin D in middle-aged Caucasians – a cross-sectional study

Cited by 11 publications

References 24 publications

Low free 25-hydroxyvitamin D and high vitamin D binding protein and parathyroid hormone in obese Caucasians. A complex association with bone?

Low free 25-hydroxyvitamin D and high vitamin D binding protein and parathyroid hormone in obese Caucasians. A complex association with bone?

Genetic Variation of the Vitamin D Binding Protein Affects Vitamin D Status and Response to Supplementation in Infants

Distribution and Determinants of Vitamin D-Binding Protein, Total, “Non-Bioavailable”, Bioavailable, and Free 25-Hydroxyvitamin D Concentrations among Older Adults

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