Phenotypic polymorphism and gender-related differences of CYP1A2 activity in a Chinese population.
OBJECTIVE
To investigate the distribution characteristics of CYP1A2 in a Chinese population, and to examine gender-related differences in CYP1A2 activity.


METHODS
Two hundred and twenty-nine healthy subjects, 120 men and 109 women, were enrolled in this study. CYP1A2 activity was measured by plasma paraxanthine/caffeine (1,7X/1,3,7X) ratio 6 h after administration of 300 mg caffeine. The concentrations of paraxanthine and caffeine in plasma were detected by h.p.l.c.


RESULTS
A 16-fold variation of CYP1A2 activity (range 0. 09 to 1.46) was shown in this study. The coefficient of variation (CV %) of CYP1A2 activity was 62.9%. Non-normal distribution of CYP1A2 activity was indicated by the Shapiro-Wilk test (P<0.001). Probit plots of CYP1A2 activity revealed a bimodal distribution with breakpoint of 1,7X/1,3,7X ratio of 0.12. The percentage of poor metabolizers (PMs) was 5.24% (95% CI: 2.35% approximately 8.13%) in this Chinese population. Residual analysis of the data also supported bimodality (P<0.01). The CYP1A2 activity of men was higher than that of women (median: 0.33 vs 0.23, P<0.001). A probit plot of CYP1A2 activity in men was shifted to the left compared with that in women. Based on phenotype, the gender-related difference was observed in extensive metabolizers (EMs) (P<0.001), but not in PMs (P >0.1). In addition, there was no sex-related difference in the incidence of PMs (P >0.1).


CONCLUSIONS
There is a phenotypic polymorphism in CYP1A2 activity in this Chinese population, and CYP1A2 activity is higher in men than that in women.
Ou-Yang
D S
DS
Pharmacogenetics Research Institute, Hunan Medical University, Changsha, Hunan, People's Republic of China.
Huang
S L
SL
Wang
W
W
Xie
H G
HG
Xu
Z H
ZH
Shu
Y
Y
Zhou
H H
HH
D000293:Adolescent; D000328:Adult; D002110:Caffeine / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics; D002681:China; D002851:Chromatography, High Pressure Liquid; D019388:Cytochrome P-450 CYP1A2 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D003627:Data Interpretation, Statistical; D005260:Female; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D010641:Phenotype; D011110:Polymorphism, Genetic; D012737:Sex Factors; D013806:Theophylline / Q000097:blood / Q000378:metabolism
D002110:Caffeine; D013806:Theophylline; D019388:Cytochrome P-450 CYP1A2; C021183:1,7-dimethylxanthine