A wide interindividual variability of urinary 6beta-hydroxycortisol to free cortisol in 487 healthy Japanese subjects in near basal condition.
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.
Inagaki
Kazuhiro
K
Pharmaceutical Information Center, Meijo University, Japan. kinagaki@ccmfs.miejo-u.ac.jp
Inagaki
Masami
M
Kataoka
Tomomi
T
Sekido
Izumi
I
Gill
Mark A
MA
Nishida
Mikio
M
D000293:Adolescent; D000328:Adult; D002851:Chromatography, High Pressure Liquid; D003404:Creatinine / Q000652:urine; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000031:analogs & derivatives* / Q000652:urine*; D007564:Japan; D008297:Male; D012016:Reference Values; D012044:Regression Analysis; D012727:Sex Characteristics
C001380:6 beta-hydroxycortisol; D003404:Creatinine; D006854:Hydrocortisone