Department of Genetics & Genomic Sciences, Box 1497, Mount Sinai School of Medicine, 1428 Madison Avenue, New York, NY 10029, USA.
Pharmacogenomics. 2012 Feb;13(3):297-307. doi: 10.2217/pgs.11.156. Epub 2011 Dec 21.
To determine if copy number variants contribute to warfarin dose requirements, we investigated CYP2C9, VKORC1, CYP4F2, GGCX and CALU for deletions and duplications in a multiethnic patient population treated with therapeutic doses of warfarin.
PATIENTS & METHODS: DNA samples from 178 patients were subjected to copy number analyses by multiplex ligation-dependent probe amplification or quantitative PCR assays. Additionally, the CYP2C9 exon 8 insertion/deletion polymorphism (rs71668942) was examined among the patient cohort and 1750 additional multiethnic healthy individuals.
All patients carried two copies of CYP2C9 by multiplex ligation-dependent probe amplification and no exon 8 deletion carriers were detected. Similarly, quantitative PCR assays for VKORC1, CYP4F2, GGCX and CALU identified two copies in all populations.
These data indicate that copy number variants in the principal genes involved in warfarin dose variability (CYP2C9, VKORC1), including genes with lesser effect (CYP4F2, GGCX), and those that may be more relevant among certain racial groups (CALU), are rare in multiethnic populations, including African-Americans.
为了确定拷贝数变异是否导致华法林剂量需求的差异，我们对接受治疗剂量华法林治疗的多民族患者群体中的 CYP2C9、VKORC1、CYP4F2、GGCX 和 CALU 进行了缺失和重复检测。
通过多重连接依赖性探针扩增或实时定量 PCR 检测 178 例患者的 DNA 样本，以进行拷贝数分析。此外，还在患者队列和 1750 例额外的多民族健康个体中检查了 CYP2C9 外显子 8 插入/缺失多态性（rs71668942）。
所有患者经多重连接依赖性探针扩增检测均携带两个 CYP2C9 拷贝，未检测到外显子 8 缺失携带者。同样，VKORC1、CYP4F2、GGCX 和 CALU 的实时定量 PCR 检测在所有人群中均鉴定出两个拷贝。
这些数据表明，华法林剂量变异性相关的主要基因（CYP2C9、VKORC1）中的拷贝数变异，包括影响较小的基因（CYP4F2、GGCX），以及在某些种族群体中可能更相关的基因（CALU），在多民族人群中包括非裔美国人中较为罕见。
