Multi-ethnic distribution of clinically relevant CYP2C genotypes and haplotypes
| Autor: | Robert J. Desnick, Ruth Kornreich, Suparna Martis, Inga Peter, Stuart A. Scott, Jean-Sébastien Hulot |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
CYP2C9
CYP2C8 haplotype Genotype Black People Locus (genetics) CYP2C19 clinical pharmacogenetics 030204 cardiovascular system & hematology Biology White People Article Cytochrome P-450 CYP2C8 03 medical and health sciences 0302 clinical medicine Asian People Gene Frequency Genetics Humans Allele Allele frequency Genotyping 030304 developmental biology Genetic association Pharmacology 0303 health sciences Haplotype Cytochrome P-450 CYP2C19 Haplotypes Molecular Medicine Aryl Hydrocarbon Hydroxylases linkage disequilibrium |
| Zdroj: | The pharmacogenomics journal |
| ISSN: | 1473-1150 1470-269X |
| DOI: | 10.1038/tpj.2012.10 |
| Popis: | To determine CYP2C19 and CYP2C8 allele frequencies, 28 coding and/or functional variants were genotyped in 1250 African-American, Asian, Caucasian, Hispanic and Ashkenazi Jewish (AJ) individuals. The combined CYP2C19 variant allele frequencies ranged from ∼0.30 to 0.41; however, the CYP2C8 frequencies were much lower (∼0.04-0.13). After incorporating previously reported CYP2C9 genotyping results from these populations (36 total CYP2C variants), 16 multi-ethnic CYP2C haplotypes were inferred with frequencies >0.5%. Notably, the 2C19*17-2C9*1-2C8*2 haplotype was identified among African-Americans (8%) and Hispanics (2%), indicating that CYP2C19*17 does not always tag a CYP2C haplotype that encodes efficient CYP2C-substrate metabolism. The 2C19*1-2C9*2-2C8*3 haplotype was identified in all populations except African-Americans and additional novel haplotypes were identified in selected populations (for example, 2C19*2-2C9*1-2C8*4 and 2C19*4B-2C9*1-2C8*1), together indicating that both CYP2C19*17 and *2 can be linked with other CYP2C loss-of-function alleles. These results have important implications for pharmacogenomic association studies involving the CYP2C locus and are clinically relevant when administering CYP2C-substrate medications. |
| Databáze: | OpenAIRE |
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