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

Abstract

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 D-3 and suggested in vivo markers of CYP3A activity in healthy volunteers from Sweden and Korea. Plasma concentrations of 25-hydroxyvitamin D-3 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 D-3 and CYP3A enzyme activity in Swedish subjects. The plasma levels of 25-hydroxyvitamin D-3 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-3 and CYP3A activity (p=0.004). Swedes (n=65) had significantly higher 25-hydroxyvitamin D-3 levels than Koreans (n=67), 75nM compared with 31nM (p<0.001). Swedish women taking oral contraceptives (OC) (n=19) had somewhat higher plasma levels of 25-hydroxyvitamin D-3 compared with Swedish women not taking oral contraceptives (n=21), 89 and 72nM, respectively (p=0.02). In conclusion, our results suggest that the overall influence on the CYP3A activity by 25-hydroxyvitamin D-3 is of marginal importance.