Vitamin D binding protein: a polymorphic protein with actin-binding capacity in COVID-19vitamin D binding protein polymorphism and COVID-19

Actin is an abundant intracellular protein that is released into the blood during tissue injury and its injection into rats causes microthrombi to form in the vasculature. This report and others have shown that actin filaments are able to aggregate platelets in an adenosine diphosphate (ADP)-dependent manner. The effects on this process of two plasma actin-binding proteins, vitamin D-binding protein (DBP) and gelsolin, were examined separately and together. The addition of DBP, a monomer-binding protein, to actin filaments did not affect their ability to induce platelet aggregation. However, severing of actin filaments with gelsolin resulted in an increased degree of platelet aggregation. Preincubation of F-actin with both gelsolin and DBP resulted in a significant inhibition of aggregation. The effects of DBP and gelsolin on actin-induced aggregation paralleled their effects on exchange of actin-bound adenine nucleotides. DBP inhibited 1, N6- ethenoadenosine 5′ triphosphate (epsilon-ATP) exchange with G-actin but not with F-actin. Gelsolin increased epsilon-ATP exchange with F-actin, which was largely abrogated by the addition of DBP. These results suggest that gelsolin's severing (and subsequent capping) of actin filaments not only results in an increase in the number of pointed filament ends but also in the dissociation of actin monomers containing ADP. Phalloidin, which stabilizes actin filaments while decreasing both monomer and nucleotide exchange, inhibited actin-induced aggregation, as well, indicating that depolymerization of actin filaments is not required to inhibit aggregation. Platelet activation by either G- or F- actin may thus be regulated by the local concentrations of the plasma actin-binding proteins gelsolin and DBP. Together, these proteins inhibit platelet aggregation in a manner that can be explained by their effects on actin's filament structure and the accessibility of its bound ADP. Depletion of DBP or gelsolin may allow actin released from injured tissues to stimulate purinergic receptors on platelets, and perhaps other cells, via its bound adenine nucleotides.

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Vitamin D binding protein, a new nutritional marker in cystic fibrosis patients

Clinical Chemistry and Laboratory Medicine (CCLM) ◽

10.1515/cclm.2008.084 ◽

2008 ◽

Vol 46 (3) ◽

Cited By ~ 29

Author(s):

Marijn M. Speeckaert ◽

Charline Wehlou ◽

Sara Vandewalle ◽

Youri E. Taes ◽

Eddy Robberecht ◽

...

Keyword(s):

Cystic Fibrosis ◽

Vitamin D ◽

Binding Protein ◽

Protein A ◽

Vitamin D Binding Protein ◽

Nutritional Marker

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Vitamin D-binding protein, a novel predictor of human labour: The relationship of serum VDBP and 25(OH)D 3

Placenta ◽

10.1016/j.placenta.2015.07.367 ◽

2015 ◽

Vol 36 (9) ◽

pp. A59-A60

Author(s):

Harry Georgiou ◽

Stella Liong ◽

Megan Di Quinzio

Keyword(s):

Vitamin D ◽

Binding Protein ◽

Protein A ◽

Vitamin D Binding Protein ◽

Human Labour ◽

Relationship Of ◽

The Relationship

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Sodium-lithium countertransport and vitamin D binding protein polymorphism in hypertension.

American Journal of Hypertension ◽

10.1016/0895-7061(96)81668-2 ◽

1996 ◽

Vol 9 (4) ◽

pp. 67A

Author(s):

D DUPREZ

Keyword(s):

Vitamin D ◽

Binding Protein ◽

Protein Polymorphism ◽

Vitamin D Binding Protein

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Associations of Vitamin D Binding Protein Gene Polymorphisms with the Development of Peripheral Arthritis and Uveitis in Ankylosing Spondylitis

The Journal of Rheumatology ◽

10.3899/jrheum.101244 ◽

2011 ◽

Vol 38 (10) ◽

pp. 2224-2229 ◽

Cited By ~ 18

Author(s):

KYONG-HEE JUNG ◽

TAE-HWAN KIM ◽

DONG-HYUK SHEEN ◽

MI-KYOUNG LIM ◽

SANG-KWANG LEE ◽

...

Keyword(s):

Vitamin D ◽

Ankylosing Spondylitis ◽

Gene Polymorphisms ◽

Binding Capacity ◽

Binding Protein ◽

Nucleotide Polymorphisms ◽

Vitamin D Binding Protein ◽

Peripheral Arthritis ◽

Goldengate Assay ◽

Increased Risk

Objective.Genetic factors account for more than 90% of overall susceptibility to ankylosing spondylitis (AS), and recent studies have focused on non-major histocompatibility complex genes. Vitamin D binding protein (DBP) is a highly polymorphic protein that transports vitamin D and its metabolites. In addition to its sterol binding capacity, DBP has many other roles in the inflammatory and immune systems, and has been reported to be associated with autoimmune diseases. We investigated the association between DBP polymorphisms and susceptibility to AS.Methods.This case-control study was conducted in 223 patients with AS and 239 ethnically matched controls who were genotyped for 8 single-nucleotide polymorphisms (SNP) in the DBP and its promoter. Genomic DNA was isolated from peripheral blood leukocytes using the standard phenolchloroform method, and the GoldenGate assay was used for genotyping.Results.No significant association was found between the susceptibility to AS and DBP polymorphisms. In a subgroup analysis of patients with AS, G alleles at rs222016 and rs222020 (OR 0.63, 95% CI 0.42–0.95, p = 0.03; OR 0.63, 95% CI 0.42–0.95, p = 0.03, respectively) and A allele at rs3733359 (OR 0.59, 95% CI 0.39–0.90, p = 0.01) showed the decreased risk of peripheral arthritis. G allele at rs4752 showed increased risk of uveitis (OR 2.04, 95% CI 1.12–3.72, p = 0.02). On the haplotype analyses, haplotype 2 (AGGA) protected against the development of peripheral arthritis (p = 0.01) and haplotype 3 (GAAG) was associated with an increased likelihood of uveitis (p = 0.02).Conclusion.DBP gene polymorphisms are associated with the development of peripheral arthritis and uveitis in Korean patients with AS. Given the influence of different DBP variants on the immune system, larger-scale studies are warranted to elucidate the role of DBP in the pathogenesis of AS.

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