“…The highest DBP serum concentration was in Gc1-1 subjects (272 ± 2 mg/L), the lowest in Gc2-2 (226 ± 2 mg/L) and intermediate levels were found in heterozygous subjects (249 ± 3 mg/L)34. Other investigators have confirmed these findings30
,
35. Similarly, our study also confirmed that the lowest serum DBP concentration was in the subjects with 436KK genotype (encoding the Gc2-2 protein variant)36.Figure 2.Common electrophoretic variants of the Gc protein (DBP).…”
Section: Introductionsupporting
confidence: 89%
“…Association was significant in separate comparisons of healthy controls with ulcerative colitis patients ( p = 0.022) and Crohn disease patients ( p = 0.016). DBP_2 TA haplotype (D432-436 K, Gc2 allele) was found at higher frequencies in healthy controls than in IBD cases [OR = 2.53, (CI = 1.48–4.34, p = 0.0005)], particularly when comparing healthy controls to the ulcerative colitis cases [OR = 4.39, (CI = 1.87–10.31, p = 0.0003)]Liver DiseaseConstans et al35
17 (15 cirrhosis; 2 hepatitis)100FranceCaucasian a
Gc1F, Gc1S, Gc2Gc1 was overrepresented in the cases versus healthy controls. An unusual electrophoretic form of Gc1 was found in many of the cases (10 out of 17 cases), perhaps differentiated by the presence of two sialic acid residues.OsteoporosisAl-oanzi et al87
56114United KingdomCaucasianVariable tandem (TAAA) n - Alu repeat in Intron8Allele *10 was associated with lower risk of osteoporosis, OR = 0.39 (CI = 0.25–0.64, p < 0.0005).…”
Section: Introductionmentioning
confidence: 99%
“…The role of DBP in ALS is not known, but it is tempting to speculate that motor neuron damage resulting in the systemic release of actin and ensuing intravascular coagulation and local hypoxia-induced oxidative damage may be mitigated by the actin-scavenging properties of DBP. Whether the apparently reduced capacity of Gc-2 for actin-scavenging, compared with Gc1
30
,
34
,
35, might increase the likelihood of disease progression is not known.…”
The vitamin D binding protein (DBP) is the major plasma carrier for vitamin D and its metabolites, but it is also an actin scavenger, and is the precursor to the immunomodulatory protein, Gc-MAF. Two missense variants of the DBP gene – rs7041 encoding Asp432Glu and rs4588 encoding Thr436Lys – change the amino acid sequence and alter the protein function. They are common enough to generate population-wide constitutive differences in vitamin D status, based on assay of the serum metabolite, 25-hydroxyvitamin D (25OHD). Whether these variants also influence the role of vitamin D in an immunologic milieu is not known. However, the issue is relevant, given the immunomodulatory effects of DBP and the role of protracted innate immune-related inflammation in response to tissue injury or repeated infection. Indeed, DBP and vitamin D may jointly or independently contribute to a variety of adverse health outcomes unrelated to classical notions of their function in bone and mineral metabolism. This review summarizes the reports to date of associations between DBP variants, and various chronic and infectious diseases. The available information leads us to conclude that DBP variants are a significant and common genetic factor in some common disorders, and therefore, are worthy of closer attention. In view of the heightened interest in vitamin D as a public health target, well-designed studies that look simultaneously at vitamin D and its carrier in relation to genotypes and adverse health outcome should be encouraged.
“…The highest DBP serum concentration was in Gc1-1 subjects (272 ± 2 mg/L), the lowest in Gc2-2 (226 ± 2 mg/L) and intermediate levels were found in heterozygous subjects (249 ± 3 mg/L)34. Other investigators have confirmed these findings30
,
35. Similarly, our study also confirmed that the lowest serum DBP concentration was in the subjects with 436KK genotype (encoding the Gc2-2 protein variant)36.Figure 2.Common electrophoretic variants of the Gc protein (DBP).…”
Section: Introductionsupporting
confidence: 89%
“…Association was significant in separate comparisons of healthy controls with ulcerative colitis patients ( p = 0.022) and Crohn disease patients ( p = 0.016). DBP_2 TA haplotype (D432-436 K, Gc2 allele) was found at higher frequencies in healthy controls than in IBD cases [OR = 2.53, (CI = 1.48–4.34, p = 0.0005)], particularly when comparing healthy controls to the ulcerative colitis cases [OR = 4.39, (CI = 1.87–10.31, p = 0.0003)]Liver DiseaseConstans et al35
17 (15 cirrhosis; 2 hepatitis)100FranceCaucasian a
Gc1F, Gc1S, Gc2Gc1 was overrepresented in the cases versus healthy controls. An unusual electrophoretic form of Gc1 was found in many of the cases (10 out of 17 cases), perhaps differentiated by the presence of two sialic acid residues.OsteoporosisAl-oanzi et al87
56114United KingdomCaucasianVariable tandem (TAAA) n - Alu repeat in Intron8Allele *10 was associated with lower risk of osteoporosis, OR = 0.39 (CI = 0.25–0.64, p < 0.0005).…”
Section: Introductionmentioning
confidence: 99%
“…The role of DBP in ALS is not known, but it is tempting to speculate that motor neuron damage resulting in the systemic release of actin and ensuing intravascular coagulation and local hypoxia-induced oxidative damage may be mitigated by the actin-scavenging properties of DBP. Whether the apparently reduced capacity of Gc-2 for actin-scavenging, compared with Gc1
30
,
34
,
35, might increase the likelihood of disease progression is not known.…”
The vitamin D binding protein (DBP) is the major plasma carrier for vitamin D and its metabolites, but it is also an actin scavenger, and is the precursor to the immunomodulatory protein, Gc-MAF. Two missense variants of the DBP gene – rs7041 encoding Asp432Glu and rs4588 encoding Thr436Lys – change the amino acid sequence and alter the protein function. They are common enough to generate population-wide constitutive differences in vitamin D status, based on assay of the serum metabolite, 25-hydroxyvitamin D (25OHD). Whether these variants also influence the role of vitamin D in an immunologic milieu is not known. However, the issue is relevant, given the immunomodulatory effects of DBP and the role of protracted innate immune-related inflammation in response to tissue injury or repeated infection. Indeed, DBP and vitamin D may jointly or independently contribute to a variety of adverse health outcomes unrelated to classical notions of their function in bone and mineral metabolism. This review summarizes the reports to date of associations between DBP variants, and various chronic and infectious diseases. The available information leads us to conclude that DBP variants are a significant and common genetic factor in some common disorders, and therefore, are worthy of closer attention. In view of the heightened interest in vitamin D as a public health target, well-designed studies that look simultaneously at vitamin D and its carrier in relation to genotypes and adverse health outcome should be encouraged.
“…The serum levete of Gc-globulin are not altered in disorders of calcium homeostasis and vitamin D deficiency or excess (4). However, decreased levels of Gc-globulin in liver disease have been reported (5)(6)(7)(8). Little attention has been given to qualitative variations of this carrier protein, but it appears that differences in the Gc-globulin phenotype distribution exist between patients with liver disease and healthy subjects (7).…”
Section: Introductionmentioning
confidence: 83%
“…Little attention has been given to qualitative variations of this carrier protein, but it appears that differences in the Gc-globulin phenotype distribution exist between patients with liver disease and healthy subjects (7). An unusual sialylatiön of the Gc l allele in patients with alcoholic cirrhosis of the liver has recently been reported (8). These reports suggest that the analysis of Gc-globulin phenotypes can be of significant value in other yet unexplored clinical situations.…”
A routine method for the analysis of Vitamin D-binding protein (Gc-globulin) phenotypes has been developed. The assay is based on isoelectric focusing in a narrow pH interval (4.5-5.4) using Agarose IEF (1%) or polyacrylamide (T5% C3%) gels, followed by immunofixation. When focused in this pH gradient the anodal and cathodal bands of the phenotype Gc 1-2 are separated by 16-18 mm. The "fast" and "slow" bands of the phenotype Gc 1-1 can also be easily distinguished from each other.The isoelectric focusing technique which has been developed resolves the Vitamin D-binding protein phenotypes in a fast, convenient and reproducible manner. Since agarose gels are so easy to cast and process, Agarose IEF is recommended äs the matrix of choice.
Hochauflösende isoelektrische Fokussierung in einem engen pH-Bereich zur Phänotypisierung des Vitamin D bindenden Proteins (Gc-Globulin)Zusammenfassung: Für die Analyse von Phänotypen des Vitamin D bindenden Proteins (Gc-Globulin) wurde eine Routine-Methode entwickelt. Der Nachweis basiert auf einer isoelektrischen Fokussierung in einem engen pH-Bereich (4,5-5,4) mit Agarose IEF (1%) oder Polyacrylamid (T5% C3%) als Matrix mit angeschlossener Immunfixation. Nach der Fokussierung in diesem pH-Gradienten sind die anodischen und kathodischen Banden des Gc-Typs 1-2 16 bis 18 mm weit voneinander getrennt. Auch die "fast" und "slow" Bande des Gc-Typs 1^-1 können leicht voneinander unterschieden werden.Die entwickelte Methode unterscheidet mit Hilfe der isoelektrischen Foktissierung die Phänotypen des Vitamin D bindenden Proteins auf schnelle, einfache und reproduzierbare Weise. Da Agarose-Gele leicht zu gießen und anzufärben sind, ist Agarose IEF die empfohlene Matrix der Wahl.
The group-specific component (GC) was discovered in 1959, and in the same year a vitamin D binding protein (DBP) in human plasma was found; however, their identity was established as late as 1975. In the GC/DBP system three common alleles, GC*1F, GC*1S, and GC*2, determine six GC phenotypes: 1F, 1S, 2, 1F-1S, 2-1F and 2-1S, these common alleles having been found in all human populations studied. In addition, more than 120 GC variants have been discovered, with varying frequencies in different populations. The distribution of the common GC phenotypes and the presence of rare GC variant phenotypes render the GC/DBP system useful for the analysis of disputed paternities.
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