A B Ruzilawati1, A W Mohd Suhaimi, S H Gan. 1. Department of Pharmacology, School of Medical Sciences, Universiti Sains Malaysia, Kelantan, Malaysia. tieimran@yahoo.com
Abstract
BACKGROUND: Cytochrome P450 3A4 (CYP3A4) is the major cytochrome involved in metabolizing of >60% of all drugs used in humans. A number of allelic variations in CYP3A4 gene are known to affect catalytic activity including CYP3A4*4, CYP3A4*5 and CYP3A4*18. We investigated the frequencies of CYP3A4*4, CYP3A4*5 and CYP3A4*18 alleles in a Malaysian population. This will impact treatment of patients receiving drugs metabolized by these alleles. METHODS: The study was conducted in 121 healthy Malaysian volunteers. DNA was extracted from leucocytes and the 3 alleles were determined by PCR-RFLP. The PCR product was later digested with restriction enzymes BstMA I, BshV I and Hpa II. RESULTS: No mutations were detected for CYP3A4*4 and CYP3A4*5 alleles. The frequency of the CYP3A4*18 allele in the Malaysian population is 2.1%. All 5 subjects with CYP3A4*18 mutations were found to be heterozygous. CONCLUSION: The present study describes polymorphisms of CYP3A4 among Malaysian subjects. Clinical relevance of these genetic variants in these healthy volunteers is under investigation.
BACKGROUND:Cytochrome P450 3A4 (CYP3A4) is the major cytochrome involved in metabolizing of >60% of all drugs used in humans. A number of allelic variations in CYP3A4 gene are known to affect catalytic activity including CYP3A4*4, CYP3A4*5 and CYP3A4*18. We investigated the frequencies of CYP3A4*4, CYP3A4*5 and CYP3A4*18 alleles in a Malaysian population. This will impact treatment of patients receiving drugs metabolized by these alleles. METHODS: The study was conducted in 121 healthy Malaysian volunteers. DNA was extracted from leucocytes and the 3 alleles were determined by PCR-RFLP. The PCR product was later digested with restriction enzymes BstMA I, BshV I and Hpa II. RESULTS: No mutations were detected for CYP3A4*4 and CYP3A4*5 alleles. The frequency of the CYP3A4*18 allele in the Malaysian population is 2.1%. All 5 subjects with CYP3A4*18 mutations were found to be heterozygous. CONCLUSION: The present study describes polymorphisms of CYP3A4 among Malaysian subjects. Clinical relevance of these genetic variants in these healthy volunteers is under investigation.
Authors: Jin Sol Lee; Hyun Sub Cheong; Lyoung Hyo Kim; Ji On Kim; Doo Won Seo; Young Hoon Kim; Myeon Woo Chung; Soon Young Han; Hyoung Doo Shin Journal: Korean J Physiol Pharmacol Date: 2013-12-16 Impact factor: 2.016