Phenotypic polymorphism and gender-related differences of CYP1A2 activity in a Chinese population

Abstract

Aims. 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: 2.35~8.13) 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.