PT - JOURNAL ARTICLE AU - Lee, Su-Jun AU - Lee, Sang Seop AU - Jung, Hyun-Ju AU - Kim, Ho-Sook AU - Park, Soo-Jin AU - Yeo, Chang-Woo AU - Shin, Jae-Gook TI - Discovery of Novel Functional Variants and Extensive Evaluation of <em>CYP2D6</em> Genetic Polymorphisms in Koreans AID - 10.1124/dmd.108.022368 DP - 2009 Jul 01 TA - Drug Metabolism and Disposition PG - 1464--1470 VI - 37 IP - 7 4099 - http://dmd.aspetjournals.org/content/37/7/1464.short 4100 - http://dmd.aspetjournals.org/content/37/7/1464.full SO - Drug Metab Dispos2009 Jul 01; 37 AB - Our objectives were to identify CYP2D6 genetic polymorphisms in a Korean population, to compare the allele frequencies with those of other ethnic groups, and to evaluate variant-induced functional variations in dextromethorphan (DM) metabolism in vitro and in vivo. Thirty-eight single nucleotide polymorphisms of CYP2D6 were identified by direct DNA sequencing in 51 Koreans. An extended set of 707 subjects were screened for the identified variants. A group of 202 healthy subjects was subjected to phenotypic analysis on DM metabolism. CYP2D6*10 was found to be the most frequent allele (45.6%), followed by CYP2D6*1 (32.3%), *2 (9.9%), *5 (5.6%), *41 (2.2%), *49 (1.4%), and some other rare alleles (&lt;1%). The newly identified E418K and S183Stop were assigned as CYP2D6*52 and CYP2D6*60, respectively, by the Human P450 (CYP) Allele Nomenclature Committee. Individuals having the CYP2D6*10/*49 genotype (n = 5) exhibited a significant decrease in CYP2D6 metabolic activity compared with those with the CYP2D6*1/*1 genotype (n = 31) (P &lt; 0.019). Variations in CYP2D6 protein levels in liver tissues (n = 49) were observed with CYP2D6 genotypes, and correlation between the CYP2D6 protein content and the activity was significant (r2 = 0.7). Given the importance of CYP2D6 in drug metabolism, subjects with the CYP2D6*10/*49 genotype may benefit from genotype analysis to achieve optimal drug therapy.