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CYP2A6 genotypes and coumarin-oxidation phenotypes in a Thai population and their relationship to tobacco smoking
Authors:Wiratchanee Mahavorasirikul  Wichittra Tassaneeyakul  Soisagwan Satarug  Ronnatrai Reungweerayut  Chacrin Na-Bangchang  Kesara Na-Bangchang
Affiliation:(1) Pharmacology and Toxicology Unit, Graduate Program in Biomedical Sciences, Faculty of Allied Health Sciences, Thammasat University, Pathumtanee, Thailand;(2) Department of Pharmacology, Khon-Kaen University, Khon-Kaen, Thailand;(3) National Research Center for Environmental Toxicology, The University of Queensland, Brisbane, Australia;(4) Mae Sot Hospital, Mae Sot, Tak Province, Thailand;(5) Department of Paediatrics, Pramongkutklao College of Medicine, Bangkok, Thailand
Abstract:Objective  To investigate the association between polymorphisms in the human CYP2A6 gene, CYP2A6 enzyme activity and the influence of cigarette smoking in a Thai population. Methods  Coumarin (5 mg capsule) was administered to 194 healthy Thai subjects. Genetic variation of the CYP2A6 gene was identified using PCR methods. The excreted dose of 7-hydroxycoumarin (as a percentage of the urine concentration) 2 h after administration was calculated as an index of coumarin metabolism. Results  The frequencies of CYP2A6 alleles *1A, *1B, *4C, *7, *8, *9 and *10 were 34.0, 35.3, 9.3, 6.4, 0.5, 12.1 and 2.4%, respectively. Of the 194 subjects tested, the number (percentages) of Thai participants classified as ultra-rapid, extensive, intermediate and poor metabolizers were 8 (4.1%), 159 (82.0%) 22 (11.3%) and five (2.6%), respectively. Conclusion  A relationship between the interindividual differences in coumarin metabolism and genetic polymorphisms of the CYP2A6 gene was observed.
Keywords:Cytochrome P450  Genetic polymorphism  Genotyping–  phenotyping  Coumarin 7-hydroxylation
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