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. (11th April 2014)

• Record Type: Journal Article
• Authors: Nylén, Hanna; Björkhem‐Bergman, Linda; Ekström, Lena; Roh, Hyung‐Keun; Bertilsson, Leif; Eliasson, Erik; Lindh, Jonatan D.; Diczfalusy, Ulf
• Is Part Of: Basic & clinical pharmacology & toxicology. Volume 115:Number 4(2014:Apr.)
• Page Start: 366
• Page End: 371
• Publication Date: 2014-04-11
• Subjects: Pharmacology -- Periodicals; Toxicology -- Periodicals; Pharmacology -- Periodicals; Toxicology -- Periodicals; Pharmacology, Clinical -- Periodicals; Computer network resources; Electronic journals; 615.1
• DOI: 10.1111/bcpt.12230
• Languages: English
• ISSNs: 1742-7835

Abstract

<abstract abstract-type="main" id="bcpt12230-abs-0001"> <title>Abstract</title> <p> <italic>In vitro</italic> 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 D<sub>3</sub> and suggested <italic>in vivo</italic> markers of CYP3A activity in healthy volunteers from Sweden and Korea. Plasma concentrations of 25‐hydroxyvitamin D<sub>3</sub> were analysed in samples from three previously performed studies, and the correlation between these levels and suggested <italic>in vivo</italic> 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 D<sub>3</sub> and CYP3A enzyme activity in Swedish subjects. The plasma levels of 25‐hydroxyvitamin D<sub>3</sub> 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 D<sub>3</sub> and CYP3A activity (<italic>p </italic>= 0.004). Swedes (n = 65) had significantly higher 25‐hydroxyvitamin D<sub>3</sub> levels than Koreans (n = 67), 75 nM compared with 31 nM (<italic>p </italic>< 0.001). Swedish women taking oral contraceptives (OC) (n = 19) had somewhat higher plasma levels of 25‐hydroxyvitamin D<sub>3</sub> compared with Swedish women not taking oral contraceptives (n = 21), 89 and 72 nM, respectively (<italic>p </italic>= 0.02). In conclusion, our results suggest that the overall influence on the CYP3A activity by 25‐hydroxyvitamin D<sub>3</sub> is of marginal importance.</p> </abstract>