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.

Original languageEnglish (US)
Pages (from-to)667-676
Number of pages10
JournalTranslational Research
Volume165
Issue number6
DOIs
StatePublished - Jun 1 2015

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Vitamin D-Binding Protein
Blood Proteins
Protein Isoforms
Vitamin D
Plasmas
Assays
24,25-Dihydroxyvitamin D 3
Calcifediol
Immunosorbents
Pulmonary diseases
High performance liquid chromatography
Oral Contraceptives
Metabolites
Tandem Mass Spectrometry
African Americans
Bone Density
Chronic Obstructive Pulmonary Disease
Minerals
Mass spectrometry
Lung Neoplasms

All Science Journal Classification (ASJC) codes

  • Public Health, Environmental and Occupational Health
  • Biochemistry, medical
  • Physiology (medical)

Cite this

Wilson, Robin ; Bortner, James D. ; Roff, Alanna ; Das, Arunangshu ; Battaglioli, Eric J. ; Richie, John ; Barnholtz-Sloan, Jill ; Chinchilli, Vernon ; Berg, Arthur ; Liu, Guodong ; Salzberg, Anna C. ; El-Bayoumy, Karam. / Genetic and environmental influences on plasma vitamin D binding protein concentrations. In: Translational Research. 2015 ; Vol. 165, No. 6. pp. 667-676.
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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.",
author = "Robin Wilson and Bortner, {James D.} and Alanna Roff and Arunangshu Das and Battaglioli, {Eric J.} and John Richie and Jill Barnholtz-Sloan and Vernon Chinchilli and Arthur Berg and Guodong Liu and Salzberg, {Anna C.} and Karam El-Bayoumy",
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Genetic and environmental influences on plasma vitamin D binding protein concentrations. / Wilson, Robin; Bortner, James D.; Roff, Alanna; Das, Arunangshu; Battaglioli, Eric J.; Richie, John; Barnholtz-Sloan, Jill; Chinchilli, Vernon; Berg, Arthur; Liu, Guodong; Salzberg, Anna C.; El-Bayoumy, Karam.

In: Translational Research, Vol. 165, No. 6, 01.06.2015, p. 667-676.

Research output: Contribution to journalArticle

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T1 - Genetic and environmental influences on plasma vitamin D binding protein concentrations

AU - Wilson, Robin

AU - Bortner, James D.

AU - Roff, Alanna

AU - Das, Arunangshu

AU - Battaglioli, Eric J.

AU - Richie, John

AU - Barnholtz-Sloan, Jill

AU - Chinchilli, Vernon

AU - Berg, Arthur

AU - Liu, Guodong

AU - Salzberg, Anna C.

AU - El-Bayoumy, Karam

PY - 2015/6/1

Y1 - 2015/6/1

N2 - 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.

AB - 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.

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