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• W2146016871 abstract "The objectives of this study were to identify the genetic variants of <i>CYP2C8</i>, analyze <i>CYP2C8</i> single nucleotide polymorphisms (SNPs), and characterize their functional consequences in the CYP2C8 substrate drug rosiglitazone in humans. The direct full sequencing of <i>CYP2C8</i> genomic DNA was performed in a Korean population (<i>n</i> = 50). A total of 17 <i>CYP2C8</i> variants including a novel coding variant (E274Stop) were identified. The novel CYP2C8 E274Stop variant was assigned as <i>CYP2C8</i>*<i>11</i> by the Human Cytochrome P450 (<i>CYP</i>) Allele Nomenclature Committee. Seventeen SNPs were used to characterize linkage disequilibrium, haplotype structures, and haplotype tagging SNPs. Genotyping for <i>CYP2C8</i>*<i>11</i> in an extended set of Koreans (<i>n</i> = 400), whites (<i>n</i> = 100), Han Chinese (<i>n</i> = 348), Vietnamese (<i>n</i> = 100), and African Americans (<i>n</i> = 93) was performed by a newly developed pyrosequencing method. The frequency of <i>CYP2C8</i>*<i>11</i> was 0.3% in Koreans, 1% in Vietnamese, and 0.14% in Chinese. However, none of the whites or African Americans contained the <i>CYP2C8</i>*<i>11</i> allele. Subjects with <i>CYP2C8</i>*<i>1</i>/*<i>11</i> exhibited higher plasma concentration-time profiles of rosiglitazone than those of nine control subjects carrying <i>CYP2C8</i>*<i>1</i>/*<i>1</i>. The area under the concentration-time curve and peak plasma concentration of rosiglitazone in individuals carrying <i>CYP2C8</i>*<i>1</i>/*<i>11</i> (<i>n</i> = 5) were 54 and 34% higher than the mean values observed in the control subjects carrying <i>CYP2C8</i>*<i>1</i>/*<i>1</i> (<i>P</i> = 0.015 and <i>P</i> = 0.025, respectively). In summary, this is the first report to characterize the allele frequency and haplotype distribution of <i>CYP2C8</i> in a Korean population, and it provides functional analysis of a new variant <i>CYP2C8</i>*<i>11</i>. Our findings suggest that individuals carrying <i>CYP2C8</i>*<i>11</i>, a null allele found in Asians only, may have lower activity for metabolizing CYP2C8 substrate drugs." @default.
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• W2146016871 date "2011-01-18" @default.
• W2146016871 modified "2023-09-25" @default.
• W2146016871 title "Discovery of a Novel Allelic Variant of <i>CYP2C8</i>, <i>CYP2C8</i>*<i>11</i>, in Asian Populations and Its Clinical Effect on the Rosiglitazone Disposition In Vivo" @default.
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• W2146016871 doi "https://doi.org/10.1124/dmd.110.035899" @default.
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