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Phenotypic polymorphism of CYP2A6 activity in a Chinese population
Ping Xu1, Song-Lin Huang, Rong-Hua Zhu
1Pharmacogenetics Research Institute, Xiang-Ya School of Medicine, Central South University, Changsha, Hunan 410078, China.
Aims:
To investigate the distribution characteristics of CYP2A6 activity in a Chinese population and to examine the sex-related differences in CYP2A6 activities.
Methods:
One hundred and twenty healthy volunteers, 63 men and 57 women, were included in the study. Cytochrome P450 (CYP) 2A6 activity was measured using the ratio of urinary 7-hydroxycoumarin (7-OHC) excreted in 8 h after a coumarin dose. The concentrations of 7-OHC in urine were determined using high performance liquid chromatography.
Results:
A 300-fold interindividual variation of CYP2A6 activity was shown in the studied Chinese population. The coefficient of variation of CYP2A6 activity was 27.2%. A Kolmogorov-Smirnov test indicated a non-normal distribution of CYP2A6 activity ( P<0.001). Probit plots of CYP2A6 activity revealed a bimodal distribution with breakpoint of activity index near 0.47. The percentage of poor metabolizers (PMs) was 13.3% (95% confidence interval 7.3%-19.4%) in this population. Residual analysis also supported bimodality ( P<0.01). The CYP2A6 activities of females were obviously higher than those of males when the activity index was less than 0.74, although no statistically significant difference in the activity index of CYP2A6 between males and females was found. However, there was no sex-related difference in the incidence of PMs ( P>0.5).
Conclusions:
There are pronounced interindividual variations and phenotypic polymorphism of CYP2A6 activities in the Chinese population.