Novel mutations in the cytochrome P450 2C19 gene: a pitfall of the PCR-RFLP method for identifying a common mutation
详细信息 查看全文
- 作者：Yumiko Ohkubo ; Akihito Ueta ; Naoki Ando ; Tetsuya Ito ; Sachiko Yamaguchi ; Kantaro Mizuno ; Satoshi Sumi ; Tohru Maeda ; Daiju Yamazaki and Yukihisa Kurono ; et al.
- 关键词：CYP2C19 ; PCR ; RFLP ; Diazepam ; Extensive metabolizers ; Poor metabolizers
- 刊名：Journal of Human Genetics
- 出版年：2006
- 出版时间：February 2006
- 年：2006
- 卷：51
- 期：2
- 页码：118-123
- 全文大小：276 KB
文摘
CYP2C19 is a clinically important enzyme involved in the metabolism of therapeutic drugs such as (S)-mephenytoin, omeprazole, proguanil, and diazepam. Individuals can be characterized as either extensive metabolizers (EM) or poor metabolizers (PM) on the basis of CYP2C19 enzyme activity. The PM phenotype occurs in 2–5 % of Caucasian populations, but at higher frequencies (18–23 % ) in Asians. CYP2C19*2 and CYP2C19*3, which are single-nucleotide polymorphisms of CYP2C19, are the main cause of PM phenotyping in homozygotes or compound heterozygotes. We report two novel mutations in the CYP2C19 gene identified by direct sequencing and subcloning procedures. One of these mutations was considered to be CYP2C19*3 by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). This result suggests that mutations classed as CYP2C19*3 might include other mutations. Further studies are needed to clarify the relationship between these novel mutations and enzyme activity.