Title: The vitamin D receptor gene FokI polymorphism: functional impact on the immune system
Authors: van Etten, Evelyne
Verlinden, Lieve
Giulietti, Annapaula
Ramos-Lopez, Elizabeth
Branisteanu, Dumitru D
Ferreira, Gabriela B
Overbergh, Lutgart
Verstuyf, Annemieke
Bouillon, Roger
Roep, Bart O
Badenhoop, Klaus
Mathieu, Chantal # ×
Issue Date: 20-Feb-2007
Publisher: Wiley-VCH
Series Title: European Journal of Immunology vol:37 issue:2 pages:395-405
Abstract: 1Alpha,25-dihydroxyvitamin D3 (1,25(OH)2D3) has important effects on the growth and function of multiple cell types. These pleiotropic effects of 1,25(OH)2D3 are mediated through binding to the vitamin D receptor (VDR). Several polymorphisms of the human VDR gene have been identified, with the FokI polymorphism resulting in VDR proteins with different structures, a long f-VDR or a shorter F-VDR. The aim of this study was to investigate the functional consequences of the FokI polymorphism in immune cells. In transfection experiments, the presence of the shorter F-VDR resulted in higher NF-kappaB- and NFAT-driven transcription as well as higher IL-12p40 promoter-driven transcription. Marginal differences were observed for AP-1-driven transcription, and no differential effects were observed for transactivation of a classical vitamin D-responsive element. Concordantly, in human monocytes and dendritic cells with a homozygous short FF VDR genotype, expression of IL-12 (mRNA and protein) was higher than in cells with a long ff VDR genotype. Additionally, lymphocytes with a short FF VDR genotype proliferated more strongly in response to phytohemagglutinin. Together, these data provide the first evidence that the VDR FokI polymorphism affects immune cell behavior, with a more active immune system for the short F-VDR, thus possibly playing a role in immune-mediated diseases.
ISSN: 0014-2980
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Clinical and Experimental Endocrinology
× corresponding author
# (joint) last author

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