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

Br J Clin Pharmacol. 2000 Feb;49(2):145-51. doi: 10.1046/j.1365-2125.2000.00128.x.

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% 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.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Caffeine / blood
  • Caffeine / metabolism
  • Caffeine / pharmacokinetics
  • China
  • Chromatography, High Pressure Liquid
  • Cytochrome P-450 CYP1A2 / drug effects
  • Cytochrome P-450 CYP1A2 / genetics
  • Cytochrome P-450 CYP1A2 / metabolism*
  • Data Interpretation, Statistical
  • Female
  • Humans
  • Male
  • Metabolic Clearance Rate
  • Phenotype
  • Polymorphism, Genetic
  • Sex Factors
  • Theophylline / blood
  • Theophylline / metabolism

Substances

  • Caffeine
  • Theophylline
  • Cytochrome P-450 CYP1A2
  • 1,7-dimethylxanthine