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Phenotypic polymorphism and gender‐related differences of CYP1A2 activity in a Chinese population
Author(s) -
OuYang DongShen,
Huang SongLin,
Wang Wei,
Xie HongGuang,
Xu ZhenHua,
Shu Yan,
Zhou HongHao
Publication year - 2000
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1046/j.1365-2125.2000.00128.x
Subject(s) - paraxanthine , cyp1a2 , caffeine , population , medicine , chemistry , endocrinology , biology , metabolism , environmental health , cytochrome p450
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.