Functionally relevant polymorphisms in the human nuclear vitamin D receptor gene

G. Kerr Whitfield, Lenore S. Remus, Peter Jurutka, Heike Zitzer, Anish K. Oza, Hope T L Dang, Carol A. Haussler, Michael A. Galligan, Michelle L. Thatcher, Carlos Encinas Dominguez, Mark R. Haussler

Research output: Contribution to journalArticle

290 Citations (Scopus)

Abstract

The functional significance of two unlinked human vitamin D receptor (hVDR) gene polymorphisms was evaluated in twenty human fibroblast cell lines. Genotypes at both a Fok I restriction site (F/f) in exon II and a singlet (A) repeat in exon IX (L/S) were determined, and relative transcription activities of endogenous hVDR proteins were measured using a transfected, 1,25-dihydroxyvitamin D3-responsive reporter gene. Observed activities ranged from 2-100-fold induction by hormone, with higher activity being displayed by the F and the L biallelic forms. Only when genotypes at both sites were considered simultaneously did statistically significant differences emerge. Moreover, the correlation between hVDR activity and genotype segregated further into clearly defined high and low activity groups with similar genotypic distributions. These results not only demonstrate functional relevance for both the F/f and L/S common polymorphisms in hVDR, but also provide novel evidence for a third genetic variable impacting receptor potency.

Original languageEnglish (US)
Pages (from-to)145-159
Number of pages15
JournalMolecular and Cellular Endocrinology
Volume177
Issue number1-2
DOIs
StatePublished - May 25 2001

Fingerprint

Calcitriol Receptors
Polymorphism
Genes
Genotype
Exons
L Forms
Calcitriol
Transcription
Fibroblasts
Reporter Genes
Human Activities
Cells
Hormones
Cell Line
Proteins

Keywords

  • Gene polymorphisms
  • Pharmacogenomics
  • Vitamin D receptor

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Kerr Whitfield, G., Remus, L. S., Jurutka, P., Zitzer, H., Oza, A. K., Dang, H. T. L., ... Haussler, M. R. (2001). Functionally relevant polymorphisms in the human nuclear vitamin D receptor gene. Molecular and Cellular Endocrinology, 177(1-2), 145-159. https://doi.org/10.1016/S0303-7207(01)00406-3

Functionally relevant polymorphisms in the human nuclear vitamin D receptor gene. / Kerr Whitfield, G.; Remus, Lenore S.; Jurutka, Peter; Zitzer, Heike; Oza, Anish K.; Dang, Hope T L; Haussler, Carol A.; Galligan, Michael A.; Thatcher, Michelle L.; Dominguez, Carlos Encinas; Haussler, Mark R.

In: Molecular and Cellular Endocrinology, Vol. 177, No. 1-2, 25.05.2001, p. 145-159.

Research output: Contribution to journalArticle

Kerr Whitfield, G, Remus, LS, Jurutka, P, Zitzer, H, Oza, AK, Dang, HTL, Haussler, CA, Galligan, MA, Thatcher, ML, Dominguez, CE & Haussler, MR 2001, 'Functionally relevant polymorphisms in the human nuclear vitamin D receptor gene', Molecular and Cellular Endocrinology, vol. 177, no. 1-2, pp. 145-159. https://doi.org/10.1016/S0303-7207(01)00406-3
Kerr Whitfield, G. ; Remus, Lenore S. ; Jurutka, Peter ; Zitzer, Heike ; Oza, Anish K. ; Dang, Hope T L ; Haussler, Carol A. ; Galligan, Michael A. ; Thatcher, Michelle L. ; Dominguez, Carlos Encinas ; Haussler, Mark R. / Functionally relevant polymorphisms in the human nuclear vitamin D receptor gene. In: Molecular and Cellular Endocrinology. 2001 ; Vol. 177, No. 1-2. pp. 145-159.
@article{6c025424d19e4fedade0c2896029cc1b,
title = "Functionally relevant polymorphisms in the human nuclear vitamin D receptor gene",
abstract = "The functional significance of two unlinked human vitamin D receptor (hVDR) gene polymorphisms was evaluated in twenty human fibroblast cell lines. Genotypes at both a Fok I restriction site (F/f) in exon II and a singlet (A) repeat in exon IX (L/S) were determined, and relative transcription activities of endogenous hVDR proteins were measured using a transfected, 1,25-dihydroxyvitamin D3-responsive reporter gene. Observed activities ranged from 2-100-fold induction by hormone, with higher activity being displayed by the F and the L biallelic forms. Only when genotypes at both sites were considered simultaneously did statistically significant differences emerge. Moreover, the correlation between hVDR activity and genotype segregated further into clearly defined high and low activity groups with similar genotypic distributions. These results not only demonstrate functional relevance for both the F/f and L/S common polymorphisms in hVDR, but also provide novel evidence for a third genetic variable impacting receptor potency.",
keywords = "Gene polymorphisms, Pharmacogenomics, Vitamin D receptor",
author = "{Kerr Whitfield}, G. and Remus, {Lenore S.} and Peter Jurutka and Heike Zitzer and Oza, {Anish K.} and Dang, {Hope T L} and Haussler, {Carol A.} and Galligan, {Michael A.} and Thatcher, {Michelle L.} and Dominguez, {Carlos Encinas} and Haussler, {Mark R.}",
year = "2001",
month = "5",
day = "25",
doi = "10.1016/S0303-7207(01)00406-3",
language = "English (US)",
volume = "177",
pages = "145--159",
journal = "Molecular and Cellular Endocrinology",
issn = "0303-7207",
publisher = "Elsevier Ireland Ltd",
number = "1-2",

}

TY - JOUR

T1 - Functionally relevant polymorphisms in the human nuclear vitamin D receptor gene

AU - Kerr Whitfield, G.

AU - Remus, Lenore S.

AU - Jurutka, Peter

AU - Zitzer, Heike

AU - Oza, Anish K.

AU - Dang, Hope T L

AU - Haussler, Carol A.

AU - Galligan, Michael A.

AU - Thatcher, Michelle L.

AU - Dominguez, Carlos Encinas

AU - Haussler, Mark R.

PY - 2001/5/25

Y1 - 2001/5/25

N2 - The functional significance of two unlinked human vitamin D receptor (hVDR) gene polymorphisms was evaluated in twenty human fibroblast cell lines. Genotypes at both a Fok I restriction site (F/f) in exon II and a singlet (A) repeat in exon IX (L/S) were determined, and relative transcription activities of endogenous hVDR proteins were measured using a transfected, 1,25-dihydroxyvitamin D3-responsive reporter gene. Observed activities ranged from 2-100-fold induction by hormone, with higher activity being displayed by the F and the L biallelic forms. Only when genotypes at both sites were considered simultaneously did statistically significant differences emerge. Moreover, the correlation between hVDR activity and genotype segregated further into clearly defined high and low activity groups with similar genotypic distributions. These results not only demonstrate functional relevance for both the F/f and L/S common polymorphisms in hVDR, but also provide novel evidence for a third genetic variable impacting receptor potency.

AB - The functional significance of two unlinked human vitamin D receptor (hVDR) gene polymorphisms was evaluated in twenty human fibroblast cell lines. Genotypes at both a Fok I restriction site (F/f) in exon II and a singlet (A) repeat in exon IX (L/S) were determined, and relative transcription activities of endogenous hVDR proteins were measured using a transfected, 1,25-dihydroxyvitamin D3-responsive reporter gene. Observed activities ranged from 2-100-fold induction by hormone, with higher activity being displayed by the F and the L biallelic forms. Only when genotypes at both sites were considered simultaneously did statistically significant differences emerge. Moreover, the correlation between hVDR activity and genotype segregated further into clearly defined high and low activity groups with similar genotypic distributions. These results not only demonstrate functional relevance for both the F/f and L/S common polymorphisms in hVDR, but also provide novel evidence for a third genetic variable impacting receptor potency.

KW - Gene polymorphisms

KW - Pharmacogenomics

KW - Vitamin D receptor

UR - http://www.scopus.com/inward/record.url?scp=0035946991&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035946991&partnerID=8YFLogxK

U2 - 10.1016/S0303-7207(01)00406-3

DO - 10.1016/S0303-7207(01)00406-3

M3 - Article

VL - 177

SP - 145

EP - 159

JO - Molecular and Cellular Endocrinology

JF - Molecular and Cellular Endocrinology

SN - 0303-7207

IS - 1-2

ER -