A Wide Interindividual Variability of Urinary 6β-Hydroxycortisol to Free Cortisol in 487 Healthy Japanese Subjects in Near Basal Condition

Abstract

The frequency distribution of CYP3A activity was investigated by measuring ratios of urinary 6beta-hydroxycortisol to free cortisol in 487 healthy subjects to determine whether a genetic polymorphism for this cytochrome enzyme exists in "native-born" Japanese persons. Spot urine samples (from 9:00 am to 12:00 pm) were collected for measurement of 6beta-hydroxycortisol and free cortisol by high-performance liquid chromatography with a CN column after extracting with a solid-phase column (Bond-Elut C18). The frequency distribution of the urinary 6beta-hydroxycortisol to free cortisol was widely distributed among subjects but with no clear bimodality by a probit plot. Furthermore, the frequency distribution assessed on a new normal test variable plot indicated the possible existence of a CYP3A sexual dimorphism. Mean 6beta-hydroxycortisol levels were higher in women (n = 249) than in men (n = 238) by 1.7-fold, and this difference was statistically significant (P < 0.01). These results show that a CYP3A genetic polymorphism in Japanese persons, based on 6beta-hydroxycortisol excretions, likely does not exist, but there appears to be a broad unimodal distribution of enzyme activity in the population.