Plasma Levels of 25‐Hydroxyvitamin D3 and In Vivo Markers of Cytochrome P450 3A Activity in Swedes and Koreans: Effects of a Genetic Polymorphism and Oral Contraceptives

In vitro studies have shown that vitamin D may induce several cytochrome P450 (CYP) enzymes in general and CYP3A4 in particular. The primary aim of this study was to investigate the relationship between plasma levels of 25‐hydroxyvitamin D3 and suggested in vivo markers of CYP3A activity in healthy...

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Bibliographic Details
Published in:Basic & clinical pharmacology & toxicology 2014-10, Vol.115 (4), p.366-371
Main Authors: Nylén, Hanna, Björkhem‐Bergman, Linda, Ekström, Lena, Roh, Hyung‐Keun, Bertilsson, Leif, Eliasson, Erik, Lindh, Jonatan D., Diczfalusy, Ulf
Format: Article
Language:English
Subjects:
Asian Continental Ancestry Group - genetics
Biological and medical sciences
Biomarkers - blood
Cholesterol - blood
Chromatography, Liquid
Contraceptives, Oral - administration & dosage
Cytochrome P-450 CYP3A - genetics
Cytochrome P-450 CYP3A - metabolism
European Continental Ancestry Group - genetics
Female
Genotype
Healthy Volunteers
Humans
Hydrocortisone - analogs & derivatives
Hydrocortisone - urine
Hydroxycholesterols - blood
Linear Models
Male
Medical sciences
Multivariate Analysis
Pharmacology. Drug treatments
Phenotype
Polymorphism, Genetic
Receptors, Calcitriol - genetics
Receptors, Calcitriol - metabolism
Republic of Korea
Sweden
Tandem Mass Spectrometry
Vitamin D - blood
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Summary:In vitro studies have shown that vitamin D may induce several cytochrome P450 (CYP) enzymes in general and CYP3A4 in particular. The primary aim of this study was to investigate the relationship between plasma levels of 25‐hydroxyvitamin D3 and suggested in vivo markers of CYP3A activity in healthy volunteers from Sweden and Korea. Plasma concentrations of 25‐hydroxyvitamin D3 were analysed in samples from three previously performed studies, and the correlation between these levels and suggested in vivo markers of CYP3A activity was investigated by means of nonparametric correlation. In addition, we studied the modulating effects of three vitamin D receptor promoter polymorphisms on the association between 25‐hydroxyvitamin D3 and CYP3A enzyme activity in Swedish subjects. The plasma levels of 25‐hydroxyvitamin D3 were not significantly associated with CYP3A phenotypes in any of the three studies, but after accounting for the vitamin D receptor polymorphism rs4516035, there was a significant positive association between 25‐hydroxyvitamin D3 and CYP3A activity (p = 0.004). Swedes (n = 65) had significantly higher 25‐hydroxyvitamin D3 levels than Koreans (n = 67), 75 nM compared with 31 nM (p 
ISSN:1742-7835
1742-7843
DOI:10.1111/bcpt.12230