Vitamin D-Binding Protein and its Polymorphisms as a Predictor for Metabolic Syndrome

Karuwanarint, Piyaporn; Phonrat, Benjaluck; Tungtrongchitr, Anchalee; Suriyaprom, Kanjana; Chuengsamarn, Somlak; Schweigert, Florian J.; Tungtrongchitr, Rungsunn

doi:10.2217/bmm-2018-0029

Cited by 12 publications

(9 citation statements)

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“…However, as reviewed by Malik et al (13) and Speeckaert et al (53), a large number of chronic diseases including type 1 and 2 diabetes (54–56), osteoporosis (57–59), chronic obstructive lung disease (60), endometriosis (61), inflammatory bowel disease (62), some cancers (63–66) [although see (66–68)], and tuberculosis (69) have been associated with DBP variants. Other SNPs at rs4588 have been associated with susceptibility to the metabolic syndrome (70). At the Gc1 locus (rs7041) the G allele is associated with increased susceptibility to hepatitis C viral infection (71).…”

Section: Vitamin D Binding Proteinmentioning

confidence: 99%

Vitamin D Binding Protein, Total and Free Vitamin D Levels in Different Physiological and Pathophysiological Conditions

2019

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This review focuses on the biologic importance of the vitamin D binding protein (DBP) with emphasis on its regulation of total and free vitamin D metabolite levels in various clinical conditions. Nearly all DBP is produced in the liver, where its regulation is influenced by estrogen, glucocorticoids and inflammatory cytokines but not by vitamin D itself. DBP is the most polymorphic protein known, and different DBP alleles can have substantial impact on its biologic functions. The three most common alleles—Gc1f, Gc1s, Gc2—differ in their affinity with the vitamin D metabolites and have been variably associated with a number of clinical conditions. Although DBP has a number of biologic functions independent of vitamin D, its major biologic function is that of regulating circulating free and total levels of vitamin D metabolites. 25 hydroxyvitamin D (25(OH)D) is the best studied form of vitamin D as it provides the best measure of vitamin D status. In a normal non-pregnant individual, approximately 0.03% of 25(OH)D is free; 85% is bound to DBP, 15% is bound to albumin. The free hormone hypothesis postulates that only free 25(OH)D can enter cells. This hypothesis is supported by the observation that mice lacking DBP, and therefore with essentially undetectable 25(OH)D levels, do not show signs of vitamin D deficiency unless put on a vitamin D deficient diet. Similar observations have recently been described in a family with a DBP mutation. This hypothesis also applies to other protein bound lipophilic hormones including glucocorticoids, sex steroids, and thyroid hormone. However, tissues expressing the megalin/cubilin complex, such as the kidney, have the capability of taking up 25(OH)D still bound to DBP, but most tissues rely on the free level. Attempts to calculate the free level using affinity constants generated in a normal individual along with measurement of DBP and total 25(OH)D have not accurately reflected directly measured free levels in a number of clinical conditions. In this review, we examine the impact of different clinical conditions as well as different DBP alleles on the relationship between total and free 25(OH)D, using only data in which the free 25(OH)D level was directly measured. The major conclusion is that a number of clinical conditions alter this relationship, raising the question whether measuring just total 25(OH)D might be misleading regarding the assessment of vitamin D status, and such assessment might be improved by measuring free 25(OH)D instead of or in addition to total 25(OH)D.

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Section: Vitamin D Binding Proteinmentioning

confidence: 99%

Vitamin D Binding Protein, Total and Free Vitamin D Levels in Different Physiological and Pathophysiological Conditions

2019

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“…Differences in these alleles were not found to contribute to a difference in fracture rate in a large study including African Americans and Caucasians (52) (62), some cancers (63)(64)(65)(66) [although see (66)(67)(68)], and tuberculosis (69) have been associated with DBP variants. Other SNPs at rs4588 have been associated with susceptibility to the metabolic syndrome (70). At the Gc1 locus (rs7041) the G allele is associated with increased susceptibility to hepatitis C viral infection (71).…”

Section: Biologic Functionmentioning

confidence: 99%

Vitamin D Binding Protein, Total and Free Vitamin D Levels in Different Physiological and Pathophysiological Conditions

2020

Frontiers Research Topics

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This review focuses on the biologic importance of the vitamin D binding protein (DBP) with emphasis on its regulation of total and free vitamin D metabolite levels in various clinical conditions. Nearly all DBP is produced in the liver, where its regulation is influenced by estrogen, glucocorticoids and inflammatory cytokines but not by vitamin D itself. DBP is the most polymorphic protein known, and different DBP alleles can have substantial impact on its biologic functions. The three most common alleles-Gc1f, Gc1s, Gc2-differ in their affinity with the vitamin D metabolites and have been variably associated with a number of clinical conditions. Although DBP has a number of biologic functions independent of vitamin D, its major biologic function is that of regulating circulating free and total levels of vitamin D metabolites. 25 hydroxyvitamin D (25(OH)D) is the best studied form of vitamin D as it provides the best measure of vitamin D status. In a normal non-pregnant individual, approximately 0.03% of 25(OH)D is free; 85% is bound to DBP, 15% is bound to albumin. The free hormone hypothesis postulates that only free 25(OH)D can enter cells. This hypothesis is supported by the observation that mice lacking DBP, and therefore with essentially undetectable 25(OH)D levels, do not show signs of vitamin D deficiency unless put on a vitamin D deficient diet. Similar observations have recently been described in a family with a DBP mutation. This hypothesis also applies to other protein bound lipophilic hormones including glucocorticoids, sex steroids, and thyroid hormone. However, tissues expressing the megalin/cubilin complex, such as the kidney, have the capability of taking up 25(OH)D still bound to DBP, but most tissues rely on the free level. Attempts to calculate the free level using affinity constants generated in a normal individual along with measurement of DBP and total 25(OH)D have not accurately reflected directly measured free levels in a number of clinical conditions. In this review, we examine the impact of different clinical conditions as well as different DBP alleles on the relationship between total and free 25(OH)D, using only data in which the free 25(OH)D level was directly measured. The major conclusion is that a number of clinical conditions alter this relationship, raising the question whether measuring just total 25(OH)D might be misleading regarding the assessment of vitamin D status, and such assessment might be improved by measuring free 25(OH)D instead of or in addition to total 25(OH)D.Keywords: vitamin D binding protein, vitamin D, free 25(OH)D, free hormone hypothesis, megalin, polymorphisms, liver cirrhosis, pregnancy Bikle and Schwartz DBP and Free 25(OH)D

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“…В последние годы различными исследовательскими группами было изучено большое число факторов, которые потенциально могут ассоциироваться с риском МС [6][7][8][9]. Особое место среди них занимают адипоцитокины (лептин, адипонектин, оментин-1, резистин и др.…”

Section: Introductionunclassified

Interaction of high-molecular-weight adiponectin concentration in blood serum with the risk of metabolic syndrome in women

Belyaeva

Brovin²,

Беркович

et al. 2021

The Scientific Notes of the Pavlov university

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Introduction. The development of metabolic syndrome (MS) in patients with abdominal obesity (AO) may be associated with a low level of the adiponectin (AN) - protective adipocytokine. AN circulates in the blood in various molecular forms.The high molecular weight AN is assumed to have greater metabolic activity. It is currently not clear what level of high molecular weight adiponectin (HMWA) in women with AO is associated with MS and its components.The objective was to study the role of high molecular weight adiponectin in the development of metabolic syndrome in women with abdominal obesity.Methods and materials. 302 women with AO and 161 women without AO were examined. MS was diagnosed in 62.3 % of patients.Results. The concentration of total adiponectin (TAN) and HMAN in the blood serum in women with MS was lower than in patients without MS (p<0.05). According to logistic regression analysis, the most significant factors influencing the risk of MS were low concentration of HMAN in the blood, age, and body mass index (p <0.05).Conclusions. It was found that women with AO and HMAN concentration of less than 1.96 μg/ml in the blood had an increased risk of metabolic syndrome.

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Vitamin D-Binding Protein and its Polymorphisms as a Predictor for Metabolic Syndrome

Abstract: GC-globulin concentrations and variation in GC rs4588 were supported as a risk factor for MetS in Thais.

Cited by 12 publications

References 30 publications

Vitamin D Binding Protein, Total and Free Vitamin D Levels in Different Physiological and Pathophysiological Conditions

Vitamin D Binding Protein, Total and Free Vitamin D Levels in Different Physiological and Pathophysiological Conditions

Vitamin D Binding Protein, Total and Free Vitamin D Levels in Different Physiological and Pathophysiological Conditions

Interaction of high-molecular-weight adiponectin concentration in blood serum with the risk of metabolic syndrome in women

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