Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine, New York, NY 10029, USA.
Pharmacogenomics J. 2013 Aug;13(4):369-77. doi: 10.1038/tpj.2012.10. Epub 2012 Apr 10.
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 2C1917-2C91-2C82 haplotype was identified among African-Americans (8%) and Hispanics (2%), indicating that CYP2C1917 does not always tag a CYP2C haplotype that encodes efficient CYP2C-substrate metabolism. The 2C191-2C92-2C83 haplotype was identified in all populations except African-Americans and additional novel haplotypes were identified in selected populations (for example, 2C192-2C91-2C84 and 2C194B-2C91-2C81), together indicating that both CYP2C1917 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.
为了确定 CYP2C19 和 CYP2C8 等位基因频率，在 1250 名非裔美国人、亚洲人、白种人、西班牙裔和阿什肯纳兹犹太人（AJ）个体中对 28 个编码和/或功能变体进行了基因分型。合并的 CYP2C19 变体等位基因频率范围为∼0.30 至 0.41；然而，CYP2C8 频率要低得多（∼0.04-0.13）。在纳入这些人群之前报道的 CYP2C9 基因分型结果（总共 36 个 CYP2C 变体）后，推断出 16 个多民族 CYP2C 单倍型，其频率>0.5%。值得注意的是，在非裔美国人（8%）和西班牙裔（2%）中发现了 2C1917-2C91-2C82 单倍型，表明 CYP2C1917 并不总是标记编码高效 CYP2C-底物代谢的 CYP2C 单倍型。除了非裔美国人和在选定人群中发现了其他新型单倍型（例如 2C192-2C91-2C83 和 2C194B-2C91-2C81）之外，在所有人群中都发现了 2C191-2C92-2C83 单倍型，这表明 CYP2C1917 和*2 都可以与其他 CYP2C 失活等位基因相关联。这些结果对涉及 CYP2C 基因座的药物基因组学关联研究具有重要意义，并且在给予 CYP2C 底物药物时具有临床相关性。
