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Vitamin D Binding Protein (VDBP) and Its Gene Polymorphisms-The Risk of Malignant Tumors and Other Diseases.

ABSTRACT: Vitamin D is an important component of the endocrine system that controls calcium homeostasis and bone mineralization. Because of the very short half-life of free serum vitamin D it is stabilized and transported to target tissues by being bound to the vitamin D binding protein (VDBP). The most common polymorphisms: rs4588 and rs7041 in the vitamin D binding protein gene may correlate with differences in vitamin D status in the serum. This review presents data that relate to the presence of genetic variants in the VDBP gene in correlation with certain diseases, mostly concerning cancers (breast, prostate, pancreatic, lung, colorectal, basal cell carcinoma cancer and cutaneous melanoma) or other related diseases (thyroid autoimmunity disorders, obesity, diabetes mellitus, bone metabolism, rheumatoid arthritis, ankylosing spondylitis, asthma, chronic obstructive pulmonary disease, tuberculosis and coronary artery diseases).

SUBMITTER: Rozmus D

PROVIDER: S-EPMC7659952 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Vitamin D Binding Protein (VDBP) and Its Gene Polymorphisms-The Risk of Malignant Tumors and Other Diseases.

Rozmus Dominika D Ciesielska Alicja A Płomiński Janusz J Grzybowski Roman R Fiedorowicz Ewa E Kordulewska Natalia N Savelkoul Huub H Kostyra Elżbieta E Cieślińska Anna A

International journal of molecular sciences 20201022 21

Vitamin D is an important component of the endocrine system that controls calcium homeostasis and bone mineralization. Because of the very short half-life of free serum vitamin D it is stabilized and transported to target tissues by being bound to the vitamin D binding protein (VDBP). The most common polymorphisms: rs4588 and rs7041 in the vitamin D binding protein gene may correlate with differences in vitamin D status in the serum. This review presents data that relate to the presence of genet ...[more]

PMID: 33105665

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Project description:BackgroundThe effects of vitamin D are exerted by interaction with the vitamin D receptor (VDR) and vitamin D binding protein (VDBP). Polymorphisms in VDR or VDBP genes may affect vitamin D levels, influencing the pathogenesis of asthma and atopy. The aim of this study was to investigate the possible association of VDR and VDBP gene single-nucleotide polymorphisms (SNP), 25-hydroxyvitamin D (25(OH)D), blood eosinophils and total IgE level in subjects with asthma in comparison with healthy individuals.MethodsThis case-control study enrolled 63 subjects with asthma (45 allergic and 18 non-allergic) and 32 healthy subjects were involved in the study. Sensitization of subjects to inhaled allergens was determined by a skin prick test, lung function was evaluated by spirometry. Blood eosinophil count was determined by standard methods. Serum 25(OH)D and total IgE levels were evaluated by ELISA. Polymorphisms in the VDR and VDBP genes on the 12q13.11 and 4q13.3 chromosomal region were analyzed using TaqMan SNP Genotyping Assay probes.ResultsIn asthma patients with vitamin D deficiency (< 20 ng/ml) the allele G of rs11168293 of VDR was more common than in those having insufficiency (20-30 ng/ml) of vitamin D (63% and 31%, p < 0.05). Moreover, asthmatic subject with rs11168293 G allele has significant higher blood eosinophil count compared to asthmatic without the rs11168293 G allele (8.5 ± 12.3% vs. 5.1 ± 1.5%, p < 0.05). Significantly higher IgE level was found in subjects with allergic asthma with the allele A of rs7041 on VDBP gene than in those without this allele (540 ± 110 and 240 ± 80 IU/ml, p < 0.05).ConclusionsThe association of polymorphisms in VDBP and VDR gene, the rs11168293 G allele and the rs7041 A allele, with 25(OH)D, blood eosinophil and total IgE level in asthma, let us suggest that vitamin D, VDR and VDBP gene polymorphisms are important in pathogenesis of asthma despite its form in relation to atopy.

Project description:BackgroundA number of polymorphisms in vitamin D binding protein (VDBP) (GC) gene have been implicated in risk of chronic obstructive pulmonary disease (COPD), but the results were controversial. GC1F, GC1S, and GC2 are three common variants of the VDBP gene [single nucleotide polymorphisms (SNPs): rs7041 and rs4588], which were reported to be associated with COPD. This study aimed to explore the association between VDBP gene polymorphisms and COPD.MethodsPubMed, EMBASE, Web of Science (Medline) and Chinese National Knowledge Infrastructure (CNKI) were searched for eligible case-control studies. Study quality was evaluated using the Newcastle-ottawa quality assessment scale (NOS). After the most appreciated genetic model was identified, a meta-analysis was performed to test the association between VDBP gene polymorphism and COPD. The pooled odds ratios (ORs) were performed respectively for the most appreciated genetic model, single allele comparison and homozygous gene model analysis. Summary receiver operating characteristic curve (SROC) analyses were applied to evaluate the diagnostic performance of polymorphism of VDBP to COPD.ResultsEight studies containing 2,216 participants were included. The analyses of the most appropriate genetic models offered significant results in recessive model of GC1F/1S group (OR =2.18), co-dominant genetic model in GC1F/2 group (1F-1F vs. 2-2: OR =4.87; 1F-2 vs. 2-2: OR =1.73; 1F-1F vs. 1F-2: OR =2.27). In single allele comparison, significant results were obtained in GC1F vs. GC1S and GC1F vs. GC2, with ORs were 1.47 and 1.77, respectively. In homozygous genes comparison, the OR was 2.51 in GC1F homozygote vs. other genotypes. Subgroup analyses offered the same significant results in Asian population, but not in Caucasian population. The SROC analyses showed the less accurate performance of polymorphism of VDBP to COPD.ConclusionsThere is a close association between COPD and GC gene polymorphisms. The GC1F allele could be a risk factor, the GC1S and GC2 allele may be protective factors in Asian, but not in Caucasians.

Dataset Information

Vitamin D Binding Protein (VDBP) and Its Gene Polymorphisms-The Risk of Malignant Tumors and Other Diseases.

Publications

Vitamin D Binding Protein (VDBP) and Its Gene Polymorphisms-The Risk of Malignant Tumors and Other Diseases.

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