Roh H K, Dahl M L, Tybring G, Yamada H, Cha Y N, Bertilsson L
Department of Medical Laboratory Sciences and Technology, Karolinska Institute, Huddinge Hospital, Sweden.
Pharmacogenetics. 1996 Dec;6(6):547-51. doi: 10.1097/00008571-199612000-00008.
Omeprazole (20 mg orally) was given to 103 healthy Korean subjects and blood was taken 3 h after administration. The plasma concentration ratio of omeprazole and hydroxyomeprazole, used as an index of CYP2C19 activity, was bimodally distributed. Thirteen subjects (12.6%) were identified as poor metabolizers (PMs) with an omeprazole hydroxylation ratio of 6.95 or higher. Among the 206 CYP2C19 alleles, CYP2C192 and CYP2C193 were found in 43 alleles (21%) and 24 alleles (12%), respectively. Twelve subjects (12%) carried two defect alleles (*2/*2, *2/*3 or *3/*3), 43 subjects (42%) were heterozygous for a mutated (*2 or *3) and a wild type (1) allele, and the remaining 48 subjects (47%) were homozygous for the wild type allele. The distributions of the metabolic ratio between these three genotype groups were significantly different (Kruskal-Wallis test: p < 0.0001). The genotypes of 19 additional Korean PMs has been identified in a previous mephenytoin study. From a total of 32 PMs, 31 were genotypically PMs by analysis of the CYP2C192 and *3 alleles and only one PM subject was found to be heterozygous for the *1 and *2 alleles. At present it cannot be judged whether this subject has a defective allele with a so-far unidentified mutation or a true wild type allele. We thus confirm a high incidence (12.6%) of PMs of omeprazole in Koreans and of the 32 Korean PMs 97% could be identified by the genotype analysis.
对103名健康韩国受试者口服给予奥美拉唑（20毫克），给药3小时后采集血样。将奥美拉唑与羟基奥美拉唑的血浆浓度比作为CYP2C19活性指标，其呈双峰分布。13名受试者（12.6%）被确定为代谢缓慢者（PMs），奥美拉唑羟化率为6.95或更高。在206个CYP2C19等位基因中，分别发现CYP2C192和CYP2C193等位基因43个（21%）和24个（12%）。12名受试者（12%）携带两个缺陷等位基因（*2/2、2/3或3/3），43名受试者（42%）为一个突变等位基因（2或3）和一个野生型等位基因（1）的杂合子，其余48名受试者（47%）为野生型等位基因纯合子。这三个基因型组之间的代谢率分布有显著差异（Kruskal-Wallis检验：p<0.0001）。在之前的美芬妥英研究中已鉴定出另外19名韩国PMs的基因型。在总共32名PMs中，通过对CYP2C192和3等位基因分析，31名在基因型上为PMs，仅发现1名PM受试者为1和2等位基因的杂合子。目前无法判断该受试者是具有迄今未鉴定突变的缺陷等位基因还是真正的野生型等位基因。因此，我们证实韩国人中奥美拉唑PMs的发生率较高（12.6%），并且在32名韩国PMs中，97%可通过基因型分析鉴定出来。
