S Y Park1, Y S Kang, M S Jeong, H K Yoon, K O Han. 1. Department of Medicine, Cheil General Hospital and Women's Healthcare Center, Kwandong University College of Medicine, Seoul, Korea.
Abstract
BACKGROUND AND OBJECTIVE: CYP3A, the drug-metabolizing enzyme is an important factor in the pharmacokinetics of many drugs. Polymorphism of the CYP3A5 gene is known to influence the functionality of the CYP3A5 enzymes. The full extent of CYP3A5 genetic polymorphism was analysed in a Korean population. METHODS: Specific polymerase chain reaction-restriction fragment length polymorphism tests for CYP 3AP1 through CYP3A5*7 or direct sequencing were used to identify reported CYP3A5 variant alleles, using 194 unrelated samples. RESULTS AND DISCUSSION: The most frequent single nucleotide polymorphism (SNP) was 6986A>G (CYP3A5*3). The next most frequent SNP was 31611C>T. Haplotype analysis using detected SNPs revealed that the most frequent haplotype was *3A (frequency: 0.724), followed by *1E (frequency: 0.211), *3C (frequency: 0.034) and *1A (frequency: 0.023). We did not find CYP3AP1*3, CYP3A5*6, or *7 in this Korean sample. CONCLUSION: A large proportion of Koreans may have relatively low levels of metabolically active CYP3A5 protein and therefore may be at risk of high levels of drugs metabolized by this enzyme, after administration of conventional doses.
BACKGROUND AND OBJECTIVE:CYP3A, the drug-metabolizing enzyme is an important factor in the pharmacokinetics of many drugs. Polymorphism of the CYP3A5 gene is known to influence the functionality of the CYP3A5 enzymes. The full extent of CYP3A5 genetic polymorphism was analysed in a Korean population. METHODS: Specific polymerase chain reaction-restriction fragment length polymorphism tests for CYP 3AP1 through CYP3A5*7 or direct sequencing were used to identify reported CYP3A5 variant alleles, using 194 unrelated samples. RESULTS AND DISCUSSION: The most frequent single nucleotide polymorphism (SNP) was 6986A>G (CYP3A5*3). The next most frequent SNP was 31611C>T. Haplotype analysis using detected SNPs revealed that the most frequent haplotype was *3A (frequency: 0.724), followed by *1E (frequency: 0.211), *3C (frequency: 0.034) and *1A (frequency: 0.023). We did not find CYP3AP1*3, CYP3A5*6, or *7 in this Korean sample. CONCLUSION: A large proportion of Koreans may have relatively low levels of metabolically active CYP3A5 protein and therefore may be at risk of high levels of drugs metabolized by this enzyme, after administration of conventional doses.
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