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Interindividual variability of cytochrome P450 (CYP) 3A inhibition by grapefruit juice was investigated in relation to CYP3A5 and multidrug resistance gene (MDR) 1 genetic polymorphisms in Chinese Han, Uygur, and Kazakh healthy subjects. The measurement of urinary 6β-hydroxycortisol/cortisol ratio was used to evaluate CYP3A activity in vivo by high-performance liquid chromatography CYP3A5 *3 and MDR1 C1236T, G2677T/A, and C3435T polymorphisms were analyzed by polymerase chain reaction restriction fragment length polymorphism. After grapefruit juice intake, urinary ratios significantly decreased in 3 Chinese ethnic groups (P < .001). Kazakh had a larger decrease of urinary ratio compared to that of Han (P < .05), and the latter had similar decrease with Uygur. Furthermore, Chinese healthy subjects carrying CYP3A5*3/*3 and MDR11236-2677-3435 T-T-T/T-T-T genotypes were found to have the largest reduction of urinary ratio (mean, 61.4%; 95% confidence interval, 53.4%-69.5%), whereas *1/*3 subjects carrying MDR11236-2677-3435 C-G-C/C-G-C genotypes had the lowest reduction (mean, 25.9%; 95% confidence interval, 3.1%-48.8%; P < .01). In conclusion, both CYP3A5*3 and MDRl variants influenced the extent of CYP3A inhibition by grapefruit juice in Chinese healthy subjects. The genetic variations influencing the CYP3A inhibitive phenotype might be helpful to explain the individual variability of grapefruit juice-drug interactions. [ABSTRACT FROM AUTHOR]

CYP2C19 and CYP2E1 show great genetic differences between Orientals and Caucasians. The objective of this study was to investigate the genotype and allele distribution patterns of CYP2C19 and CYP2E1 polymorphisms among healthy participants in mainland Chinese Kazakh, Uygur and Han populations by the PCR–restriction fragment length polymorphism technique. The allele frequencies of CYP2C19*2, CYP2E1*5B and CYP2E1*6 were significantly lower in the Chinese Kazakh (15.4, 11.2 and 14.5%, respectively) (P<0.05) and Uygur (16.1, 12.1 and 18.8%) (P<0.05) populations than that in the Chinese Han population (28.8, 19.4 and 26.2%), but the frequencies of CYP2C19*3 were similar among the three populations (8.0, 9.4 and 7.2%). Frequencies of the three combined genotypes, one for predicted CYP2C19 poor metabolizers and two for predicted high levels of CYP2E1 transcription, were significantly lower in the Chinese Kazakh (7.5, 19.6 and 28.0%, respectively) (P<0.05, χ2-test) and Uygur (8.1, 22.8 and 33.6%) (P<0.05) populations compared with the Chinese Han population (16.5, 35.9 and 44.7%). The present research shows that frequencies of the functional single-nucleotide polymorphisms in the CYP2C19 and CYP2E1 genes vary in the Chinese Kazakh, Uygur and Han populations, suggesting that disease susceptibilities or drug responses associated with enzyme activities of CYP2C19 and CYP2E1 may differ in the diverse ethnic populations in mainland China.Journal of Human Genetics (2009) 54, 372–375; doi:10.1038/jhg.2009.41; published online 15 May 2009 [ABSTRACT FROM AUTHOR]