title: Genetic and environmental influences on plasma vitamin D binding protein concentrations.
abstract: Recent studies suggest that low vitamin D-binding protein (VDBP aka group-specific complement or Gc) concentrations may be linked with inflammatory-mediated conditions, including asthma, chronic obstructive pulmonary disease, and cancer. However, these studies may be confounded by substantial racial and ethnic or genetic differences. The purpose of this study was to test the hypothesis that circulating VDBP concentrations are significantly associated with genetic ancestry. We used a validated high-performance liquid chromatography tandem mass spectrometry assay of 25-hydroxyvitamin D3 and its downstream metabolite 24,25-dihydroxyvitamin D3. VDBP concentrations (milligrams per liter) were measured in duplicate using a commercial enzyme-linked immunosorbent assay among healthy African American (n = 56) and Caucasian American (n = 60) participants. Ancestry informative markers across the genome were used to estimate individual genetic ancestry proportions, designed to robustly distinguish between West African and European ancestry. Genotype-defined Gc isoforms were defined using rs7041 and rs4588 combination groups. VDBP concentration was correlated with both Gc isoform (r = 0.93, P < 0.001) and West African genetic ancestry (r = -0.66, P < 0.001). In the final model, Gc isoform, the catabolic ratio of serum vitamin D, oral contraceptive use, and body mass index remained significantly associated with VDBP concentration, after adjustment for genetic ancestry. Failure to adjust for Gc isoform may lead to spurious associations in studies of VDBP concentration and disease risk, particularly when the condition of interest may also be associated with genetic ancestry. The higher circulating VDBP concentrations and higher vitamin D catabolic rate among Caucasian Americans observed here appear to be consistent with lower bone mineral density and racial and ethnic differences in vitamin D-inducing cytokines.
authors.affiliation: Division of Epidemiology, Department of Public Health Sciences, Pennsylvania State University College of Medicine, Hershey, Pennsylvania. Electronic address: rwilson@psu.edu.
authors.forename: Robin Taylor
authors.initials: RT
authors.lastname: Wilson
authors.affiliation: Perelman School of Medicine, University of Pennsylvania Philadelphia, Pennsylvania.
authors.forename: James D
authors.initials: JD
authors.lastname: Bortner
authors.affiliation: Department of Biochemistry and Molecular Biology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania.
authors.forename: Alanna
authors.initials: A
authors.lastname: Roff
authors.affiliation: Department of Biochemistry and Molecular Biology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania.
authors.forename: Arunangshu
authors.initials: A
authors.lastname: Das
authors.affiliation: Division of Epidemiology, Department of Public Health Sciences, Pennsylvania State University College of Medicine, Hershey, Pennsylvania.
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Battaglioli
authors.affiliation: Division of Epidemiology, Department of Public Health Sciences, Pennsylvania State University College of Medicine, Hershey, Pennsylvania.
authors.forename: John P
authors.initials: JP
authors.lastname: Richie
authors.affiliation: Department of Epidemiology and Biostatistics, Center for Proteomics and Bioinformatics, Case Western Reserve University, Cleveland, Ohio.
authors.forename: Jill
authors.initials: J
authors.lastname: Barnholtz-Sloan
authors.affiliation: Division of Epidemiology, Department of Public Health Sciences, Pennsylvania State University College of Medicine, Hershey, Pennsylvania.
authors.forename: Vernon M
authors.initials: VM
authors.lastname: Chinchilli
authors.affiliation: Division of Epidemiology, Department of Public Health Sciences, Pennsylvania State University College of Medicine, Hershey, Pennsylvania.
authors.forename: Arthur
authors.initials: A
authors.lastname: Berg
authors.affiliation: Division of Epidemiology, Department of Public Health Sciences, Pennsylvania State University College of Medicine, Hershey, Pennsylvania.
authors.forename: Guodong
authors.initials: G
authors.lastname: Liu
authors.affiliation: Division of Epidemiology, Department of Public Health Sciences, Pennsylvania State University College of Medicine, Hershey, Pennsylvania.
authors.forename: Anna C
authors.initials: AC
authors.lastname: Salzberg
authors.affiliation: Perelman School of Medicine, University of Pennsylvania Philadelphia, Pennsylvania.
authors.forename: Karam
authors.initials: K
authors.lastname: El-Bayoumy
mesh_terms: D000328:Adult; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006801:Humans; D008297:Male; D053719:Tandem Mass Spectrometry; D014809:Vitamin D-Binding Protein / Q000097:blood*; D055815:Young Adult
chemical_list: D014809:Vitamin D-Binding Protein