Functional Characterization of Novel Allelic Variants of CYP2C9 Recently Discovered in Southeast Asians

CYP2C9 was recently resequenced in 150 Asian subjects from Singapore. Several new coding variants were reported, and these variants are now named CYP2C9*14 (R125H), CYP2C9*15 (S162X), CYP2C9*16 (T299A), CYP2C9*17 (P382S), CYP2C9*18 (D397A), and CYP2C9*19 (Q454H). The CYP2C9*18 variant also contained an I359L change previously associated with the CYP2C9*3 allele. In this study, we as-sessed the functional consequences of the new coding changes. cDNAs containing each of the new coding changes were constructed by site-directed mutagenesis and expressed in a bacterial cDNA expression system, the allelic proteins were partially purified, and their ability to hydroxylate a prototype CYP2C9 substrate was assayed. Expression of cDNAs in Esch-erichia coli containing either the D397A change or the S162