D Li1, G-L Zhang, Y-Q Lou, Q Li, X Wang, X-Y Bu. 1. Department of Pharmacology, Basic Medical School, Health Science Center, Beijing (Peking) University, Beijing, China.
Abstract
BACKGROUND AND OBJECTIVE: The drug transporter MDR1 and the drug metabolizing enzyme CYP3A are the two major biological factors determining the pharmacokinetics of many drugs. The functional MDR1 single nucleotide polymorphisms (SNPs) and a prevalent CYP3A5 SNP show marked interethnic variation among Orientals, Caucasians and Africans. In this study, we investigated the distribution of MDR1 and CYP3A5 SNPs among mainland Chinese Han, Uygur and Kazakh ethnic groups. METHODS: Genotypes of the MDR1 C1236T, G2677T/A and C3435T, and CYP3A5*3, CYP3AP1*3 SNPs were determined in 434 unrelated healthy subjects (165 Chinese Han, 161 Chinese Uygur and 108 Chinese Kazakh) using polymerase chain reaction followed by restriction fragment length polymorphism analysis. RESULTS AND DISCUSSION: A significantly higher MDR1 3435T variant frequency was observed in Uygur (52.8%), than in Kazakh (39.8%) and Han (37.9%) Chinese (P < 0.01, Fisher's exact test). There was no significant difference in MDR1 1236T and 2677T/A variant frequencies between Han, Uygur and Kazakh. CYP3A5*3 (G) allele was observed at intermediate frequencies in Uygur (84.8%) and Kazakh (86.6%), relative to Han (72.7%) and values previously reported in Caucasians (91.7%). The CYP3AP1*3 (A) allele was strongly linked to CYP3A5*3 in Chinese Han, Uygur and Kazakh. CONCLUSION: Significant interethnic differences in MDR1 haplotype and CYP3A5 variant frequencies exist between mainland Chinese Han and Caucasians, and the intermediate frequencies observed in Chinese Uygur and Kazakh might be due to the genetic admixture of Eurasians and Orientals.
BACKGROUND AND OBJECTIVE: The drug transporter MDR1 and the drug metabolizing enzyme CYP3A are the two major biological factors determining the pharmacokinetics of many drugs. The functional MDR1 single nucleotide polymorphisms (SNPs) and a prevalent CYP3A5 SNP show marked interethnic variation among Orientals, Caucasians and Africans. In this study, we investigated the distribution of MDR1 and CYP3A5 SNPs among mainland Chinese Han, Uygur and Kazakh ethnic groups. METHODS: Genotypes of the MDR1C1236T, G2677T/A and C3435T, and CYP3A5*3, CYP3AP1*3 SNPs were determined in 434 unrelated healthy subjects (165 Chinese Han, 161 Chinese Uygur and 108 Chinese Kazakh) using polymerase chain reaction followed by restriction fragment length polymorphism analysis. RESULTS AND DISCUSSION: A significantly higher MDR1 3435T variant frequency was observed in Uygur (52.8%), than in Kazakh (39.8%) and Han (37.9%) Chinese (P < 0.01, Fisher's exact test). There was no significant difference in MDR1 1236T and 2677T/A variant frequencies between Han, Uygur and Kazakh. CYP3A5*3 (G) allele was observed at intermediate frequencies in Uygur (84.8%) and Kazakh (86.6%), relative to Han (72.7%) and values previously reported in Caucasians (91.7%). The CYP3AP1*3 (A) allele was strongly linked to CYP3A5*3 in Chinese Han, Uygur and Kazakh. CONCLUSION: Significant interethnic differences in MDR1 haplotype and CYP3A5 variant frequencies exist between mainland Chinese Han and Caucasians, and the intermediate frequencies observed in Chinese Uygur and Kazakh might be due to the genetic admixture of Eurasians and Orientals.