Mean Serum Concentration of Vitamin D-binding Protein (Gc Globulin) Is Related to the Gc Phenotype in Women

Lauridsen, Anna Lis; Vestergaard, Peter; Nexø, Ebba

doi:10.1093/clinchem/47.4.753

Cited by 144 publications

(91 citation statements)

References 21 publications

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“…Commentaries in response to the Powe et al study cited prior studies that did not show race differences in circulating DBP using polyclonal assays, (35,(45)(46)(47) as well as a study that found the lowest DBP concentrations among Gc2 rather than Gc1f homozygotes using an immunonephelometric method. (48) Consistent with these studies, we did not find race or genotypic differences in serum DBP using the polyclonal ELISA. Although the polyclonal assay yielded consistently higher concentrations compared with LC-MS/MS, this was nondifferential by genotype.…”

Section: Discussionsupporting

confidence: 89%

Comparison of Two ELISA Methods and Mass Spectrometry for Measurement of Vitamin D-Binding Protein: Implications for the Assessment of Bioavailable Vitamin D Concentrations Across Genotypes

Denburg

Hoofnagle²,

Sayed

et al. 2016

Journal of Bone and Mineral Research

104

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Studies using vitamin D-binding protein (DBP) concentrations to estimate free and bioavailable vitamin D have increased dramatically in recent years. Combinations of two single-nucleotide polymorphisms produce three major DBP isoforms (Gc1f, Gc1s and Gc2). A recent study showed that DBP concentrations quantified by liquid chromatography-tandem mass spectrometry (LC-MS/MS) did not differ by race, while a widely used monoclonal ELISA quantified DBP differentially by isoform, yielding significantly lower DBP concentrations in black versus white individuals. We compared measurements of serum DBP using a monoclonal ELISA, a polyclonal ELISA, and LC-MS/MS in 125 participants in the Chronic Renal Insufficiency Cohort. Serum free and bioavailable 25OHD were calculated based on DBP concentrations from these three assays in homozygous participants, and race differences were compared. We confirmed that the monoclonal ELISA quantifies DBP differentially by isoform and demonstrated that the polyclonal ELISA is not subject to this bias. While ≤9% of the variability in DBP concentrations quantified using either LC-MS/MS or the polyclonal ELISA was explained by genotype, 85% of the variability in the monoclonal ELISA-based measures was explained by genotypes. DBP concentrations measured by the monoclonal ELISA were disproportionately lower than LC-MS/MS-based results for Gc1f homozygotes [median difference −67%; interquartile range (IQR) −71%, −64%], 95% of whom were black. In contrast, the polyclonal ELISA yielded consistently and similarly higher measurements of DBP than LC-MS/MS, irrespective of genotype, with a median percent difference of +50% [IQR +33%, +65%]. Contrary to findings using the monoclonal ELISA, DBP concentrations did not differ by race, and free and bioavailable 25OHD were significantly lower in black versus white participants based on both the polyclonal ELISA and LC-MS/MS, consistent with their lower total 25OHD. Future studies of DBP and free or bioavailable vitamin D metabolites should employ DBP assays that are not biased by DBP genotype.

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Section: Discussionsupporting

confidence: 89%

Comparison of Two ELISA Methods and Mass Spectrometry for Measurement of Vitamin D-Binding Protein: Implications for the Assessment of Bioavailable Vitamin D Concentrations Across Genotypes

Denburg

Hoofnagle²,

Sayed

et al. 2016

Journal of Bone and Mineral Research

104

View full text Add to dashboard Cite

show abstract

“…The majority of vitamin D in the circulation is bound to VDB in its biological inactive but stable form (25-OH-D) (20), where VDB transports vitamin D to target organs. There are four forms of VDB and the genetic variance in the VDB gene is associated with varying vitamin D levels (21). Independently to its carrier function, VDB also has anti-inflammatory and immune-modulatory functions (22), which add a new level to its disease involvement.…”

Section: Discussionmentioning

confidence: 99%

Cerebrospinal fluid proteome comparison between multiple sclerosis patients and controls

et al. 2012

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“…These variations were associated with lower GC-globulin circulating levels. 21 Several studies have been performed to ascertain whether GC-globulin polymorphisms influence serum vitamin D levels. 14 There is substantial agreement that the carriage of the major alleles of GC rs7041 G>T and rs4588 C>A polymorphisms, in particular the GC-1s and GC-1f isoforms, is associated with higher serum vitamin D. To assess the overall influence of the two polymorphic loci of GC-globulin on vitamin D levels, diplotype analysis was performed.…”

Section: Discussionmentioning

confidence: 99%

Vitamin D binding protein gene polymorphisms and baseline vitamin D levels as predictors of antiviral response in chronic hepatitis C

et al. 2012

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Vitamin D deficiency seems to predict the unsuccessful achievement of sustained viral response (SVR) after antiviral treatment in hepatitis C virus (HCV) difficult-to-treat genotypes. Vitamin D binding protein (GC) gene polymorphisms are known to influence vitamin D levels. This study was performed to assess whether the interaction between basal circulating vitamin D and the GC polymorphism plays a role in influencing the rate of antiviral responses in patients affected by chronic hepatitis C. In all, 206 HCV patients treated with a combination therapy of pegylated (PEG)-interferon plus ribavirin were retrospectively evaluated. GC rs7041 G>T, GC rs4588 C>A, and IL-28B rs12979860 C>T polymorphisms were genotyped. Frequencies of GC rs7041 G>T and rs4588 C>A polymorphisms were: G/G 5 64 (31.1%), G/T 5 100 (48.5%), T/T 5 42 (20.4%) and C/C 5 108 (52.4%), C/A 5 84 (40.8%), A/A 5 14 (6.8%). Patients were divided into those carrying !3 major alleles (wildtype [WT] 1: G-C/G-C, G-C/T-C, G-C/G-A, N 5 100) and the remaining (WT2: G-C/T-A, T-A/T-C, T-A/T-A, T-C/T-C, N 5 106). Four groups were identified: vitamin D 20 ng/mL and WT2, vitamin D 20 and WT1, vitamin D >20and WT2, vitamin D >20 and WT1. In difficult-to-treat HCV genotypes the proportion of patients achieving SVR significantly increased with a linear trend from the first to the last group: 6/25 (24.0%), 9/24 (37.5%), 12/29 (41.4%), 19/29 (65.5%) (P 5 0.003). At multivariate analysis, having basal vitamin D >20 ng/mL plus the carriage of GC WT1 was found to be an independent predictor of SVR (odds ratio 4.52, P 5 0.015). Conclusion: In difficult-to-treat HCV genotypes, simultaneous pretreatment normal serum vitamin D levels and the carriage of GC-globulin WT isoform strongly predicts the achievement of SVR after PEG-interferon plus ribavirin antiviral therapy. (HEPATOLOGY 2012;56:1641-1650

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Mean Serum Concentration of Vitamin D-binding Protein (Gc Globulin) Is Related to the Gc Phenotype in Women

Cited by 144 publications

References 21 publications

Comparison of Two ELISA Methods and Mass Spectrometry for Measurement of Vitamin D-Binding Protein: Implications for the Assessment of Bioavailable Vitamin D Concentrations Across Genotypes

Comparison of Two ELISA Methods and Mass Spectrometry for Measurement of Vitamin D-Binding Protein: Implications for the Assessment of Bioavailable Vitamin D Concentrations Across Genotypes

Cerebrospinal fluid proteome comparison between multiple sclerosis patients and controls

Vitamin D binding protein gene polymorphisms and baseline vitamin D levels as predictors of antiviral response in chronic hepatitis C

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