Upregulation of Irisin and Vitamin D-Binding Protein Concentrations by Increasing Maternal 25-Hydrovitamin D Concentrations in Combination with Specific Genotypes of Vitamin D-Binding Protein Polymorphisms

Dyshomeostasis of vitamin D-binding protein (VDBP) has been implicated in the pathogenesis of various pregnancy complications, including preeclampsia, preterm birth, gestational diabetes, and adverse metabolic profiles in the offspring. VDBP polymorphisms have been consistently reported to contribute to this intriguing interplay. Until recently, the effects of VDBP polymorphism heterogeneity on maternal and neonatal adipomyokine profiles have not been investigated, specifically after incorporating the different maternal and neonatal 25-hydroxyvitamin D concentration cut-offs at birth. We aimed to investigate the potential effects of maternal and neonatal VDBP polymorphisms on adiponectin, irisin, and VDBP concentrations at birth, according to different cut-offs of vitamin D status, in maternal–neonatal dyads recruited from the sunny region of Northern Greece. We obtained blood samples from 66 mother–child pairs at birth. Results indicated that (i) Neonatal serum biomarkers were not affected by any included neonatal VDBP polymorphism according to different cut-offs of neonatal vitamin D status at birth, (ii) neonatal VDBP concentration was elevated in neonates with maternal rs7041 GG genotype, (iii) maternal 25(OH)D at ≤75 nmol/L resulted in increased concentrations of maternal VBDP and irisin concentrations in women with CC genotype for rs2298850 and rs4588,whereas this effect was also evident for this cut-off for neonatal VDBP concentrations at birth for GC genotype for rs 7041, and iv) no significant effect of neonatal VDBP polymorphisms was observed on neonatal VDBP, adiponectin, or irisin levels when stratified according to maternal 25(OH)D cut-offs. In conclusion, these findings confirm that among women with the combination of CC genotype for rs2298850 and rs4588, a specific high cut-off of maternal 25(OH)D results in increasing maternal VBDP concentrations, hence providing a mechanistic rationale for aiming for specific cut-offs of vitamin D after supplementation during pregnancy, in daily clinical practice.

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Investigating the Role of Functional Polymorphism of Maternal and Neonatal Vitamin D Binding Protein in the Context of 25-Hydroxyvitamin D Cutoffs as Determinants of Maternal-Neonatal Vitamin D Status Profiles in a Sunny Mediterranean Region

Nutrients ◽

10.3390/nu13093082 ◽

2021 ◽

Vol 13 (9) ◽

pp. 3082

Author(s):

Spyridon N. Karras ◽

Erdinç Dursun ◽

Merve Alaylıoğlu ◽

Duygu Gezen-Ak ◽

Cedric Annweiler ◽

...

Keyword(s):

Vitamin D ◽

Mediterranean Region ◽

Binding Protein ◽

Hypovitaminosis D ◽

Vitamin D Status ◽

Vitamin D Binding Protein ◽

Hydroxyvitamin D ◽

High Prevalence ◽

25 Hydroxyvitamin D ◽

Causative Effect

Recent results indicate that dysregulation of vitamin D-binding protein (VDBP) could be involved in the development of hypovitaminosis D, and it comprises a risk factor for adverse fetal, maternal and neonatal outcomes. Until recently, there was a paucity of results regarding the effect of maternal and neonatal VDBP polymorphisms on vitamin D status during pregnancy in the Mediterranean region, with a high prevalence of hypovitaminosis D. We aimed to evaluate the combined effect of maternal and neonatal VDBP polymorphisms and different maternal and neonatal 25-hydroxyvitamin D (25(OH)D) cut-offs on maternal and neonatal vitamin D profile. Blood samples were obtained from a cohort of 66 mother–child pairs at birth. Our results revealed that: (i) Maternal VDBP polymorphisms do not affect neonatal vitamin D status at birth, in any given internationally adopted maternal or neonatal cut-off for 25(OH)D concentrations; (ii) neonatal VDBP polymorphisms are not implicated in the regulation of neonatal vitamin D status at birth; (iii) comparing the distributions of maternal VDBP polymorphisms and maternal 25(OH)D concentrations, with cut-offs at birth, revealed that mothers with a CC genotype for rs2298850 and a CC genotype for rs4588 tended to demonstrate higher 25(OH)D (≥75 nmol/L) during delivery (p = 0.05 and p = 0.04, respectively), after adjustments for biofactors that affect vitamin D equilibrium, including UVB, BMI and weeks of gestation. In conclusion, this study from Southern Europe indicates that maternal and neonatal VDBP polymorphisms do not affect neonatal vitamin D status at birth, whereas mothers with CC genotype for rs2298850 and CC genotype for rs4588 demonstrate higher 25(OH)D concentrations. Future larger studies are required to establish a causative effect of these specific polymorphisms in the attainment of an adequate (≥75 nmol/L) maternal vitamin D status during pregnancy.

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25-Hydroxyvitamin D, Vitamin D Binding Protein, Bioavailable 25-Hydroxyvitamin D, and Body Composition in a Diverse Sample of Women Collegiate Indoor Athletes

Journal of Functional Morphology and Kinesiology ◽

10.3390/jfmk5020032 ◽

2020 ◽

Vol 5 (2) ◽

pp. 32

Author(s):

Jennifer B. Fields ◽

Sina Gallo ◽

Jenna M. Worswick ◽

Deanna R. Busteed ◽

Margaret T. Jones

Keyword(s):

Vitamin D ◽

Body Composition ◽

Binding Protein ◽

Sport Performance ◽

Whole Body ◽

Dietary Vitamin ◽

Vitamin D Status ◽

Vitamin D Binding Protein ◽

Hydroxyvitamin D ◽

25 Hydroxyvitamin D

Women athletes are at higher risk for bone diseases; yet, information on vitamin D status ((25(OH)D), vitamin D binding protein (VDBP), and bioavailable 25(OH)D is limited. Collegiate athletes (n = 36) from volleyball (WVB), basketball (WBB), and track and field (WTF) were measured for (25(OH)D), VDBP, and bioavailable 25(OH)D; body composition and bone mineral density (BMD); and skin pigmentation. Participants self-reported daily vitamin D intake and sun exposure. One-way analysis of variance analyzed mean differences in measures across sports. Linear regression examined relationships between 25(OH)D; VDBP; bioavailable 25(OH)D; and whole body, hip, and spine BMD. Participants’ (mean ± SD, 19.4 ± 1.4 years, 172.75 ± 8.21 cm, 70.9 ± 13.2 kg, and 22.9 ± 4.1% body fat) overall mean 25(OH)D was 70.5 ± 32.25 nmol/L, and 28% of participants were deemed inadequate and 61% below thresholds identified as sufficient for athletes. Although WBB athletes consumed higher (p = 0.007) dietary vitamin D (760.9 ± 484.2 IU/d) than WVB (342.6 ± 257.8) and WTF (402.3 ± 376.4) athletes did, there were no differences across sport in serum 25(OH)D. WVB and WTF had higher bioavailable 25(OH)D than WBB. No relationships existed between vitamin D status and body composition. Vitamin D inadequacy was identified among 1/3 of women indoor sport athletes. Consistent monitoring of vitamin D status and diet are recommended to sustain athlete health and sport performance.

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Vitamin D Binding Protein and Bone Health

International Journal of Endocrinology ◽

10.1155/2014/561214 ◽

2014 ◽

Vol 2014 ◽

pp. 1-5 ◽

Cited By ~ 41

Author(s):

Ishir Bhan

Keyword(s):

Vitamin D ◽

Bone Density ◽

Bone Health ◽

Binding Protein ◽

Vitamin D Status ◽

Vitamin D Binding Protein ◽

Hydroxyvitamin D ◽

25 Hydroxyvitamin D ◽

Major Carrier ◽

Osteoclast Activation

Vitamin D binding protein (DBP) is the major carrier protein of 25-hydroxyvitamin D (25(OH) D) in the circulation, where it may serve roles in maintaining stable levels during times of decreased 25(OH) availability and in regulating delivery of 25(OH) D to target tissues. Several genetic polymorphisms of DBP have been described that lead to phenotypic changes in the protein that may affect affinity, activity, and concentration. These polymorphisms have been linked with alterations in bone density in several populations. One of the mechanisms by which DBP may alter bone health involves regulating vitamin D bioavailability. DBP-bound vitamin is thought to be relatively unavailable to target tissues, and thus alterations in DBP levels or affinity could lead to changes in vitamin D bioactivity. As a result, functional vitamin D status may differ greatly between individuals with similar total 25(OH) D levels. Additionally, DBP may have independent roles on macrophage and osteoclast activation. This review will summarize recent findings about DBP with respect to measures of bone density and health.

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

Nutrients ◽

10.3390/nu13113982 ◽

2021 ◽

Vol 13 (11) ◽

pp. 3982

Author(s):

Anna Zhu ◽

Sabine Kuznia ◽

Tobias Niedermaier ◽

Bernd Holleczek ◽

Ben Schöttker ◽

...

Keyword(s):

Older Adults ◽

Vitamin D ◽

Health Outcomes ◽

Binding Protein ◽

Vitamin D Status ◽

Linear Regression Models ◽

Vitamin D Binding Protein ◽

Hydroxyvitamin D ◽

Reactive Protein ◽

25 Hydroxyvitamin D

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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Calcium-Regulating Hormones and Minerals From Birth to 18 Months of Age: A Cross-Sectional Study. I. Effects of Sex, Race, Age, Season, and Diet on Vitamin D Status

PEDIATRICS ◽

10.1542/peds.77.6.883 ◽

1986 ◽

Vol 77 (6) ◽

pp. 883-890

Author(s):

P. Lichtenstein ◽

B. L. Specker ◽

R. C. Tsang ◽

F. Mimouni ◽

C. Gormley

Keyword(s):

Vitamin D ◽

Human Milk ◽

Binding Protein ◽

Vitamin D Metabolites ◽

Vitamin D Status ◽

Vitamin D Binding Protein ◽

Hydroxyvitamin D ◽

Dihydroxyvitamin D ◽

1,25 Dihydroxyvitamin D ◽

25 Hydroxyvitamin D

The influence of sex, race, age, season, and diet (cow's milk formula v human milk) on the vitamin D and vitamin D-binding protein status in infants less than 18 months of age was investigated in this crosssectional, prospective study of 198 infants. No differences by sex were observed in serum 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, 24,25-dihydroxyvitamin D, or vitamin D-binding protein concentrations. By race, black infants had significantly elevated serum 1,25-dihydroxyvitamin D levels relative to white infants. By age, vitamin D-binding protein concentrations increased with increasing age. By season, serum 25-hydroxyvitamin D concentrations were low in winter, whereas 1,25-dihydroxyvitamin D and vitamin D-binding protein were high in winter compared with summer. By diet, formula-fed infants had higher serum concentrations of all measured vitamin D metabolites and vitamin D-binding protein than human milk-fed infants. Thus, race, age, season, and diet exert, individually or in combination, different and significant effects on vitamin D metabolites; these should be considered in assessing infant vitamin D status.

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