Evidence that poor metabolizers of (S)-mephenytoin could be identified by haplotypes of CYP2C19 in Japanese.
Evidence that poor metabolizers of (S)-mephenytoin could be identified by haplotypes of CYP2C19 in Japanese.
复制标题
有证据表明，(S)-美芬妥英的不良代谢者可以通过日语中 CYP2C19 的单倍型来识别。
DOI：
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复制
发表时间：
1996
期刊：
影响因子：
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通讯作者：
Ikuko Kondo
中科院分区：
文献类型：
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作者：
Fumie Takakubo;Akira Kuwano;Ikuko Kondo
（S）-美芬妥英通过CYP 2C 19代谢。本研究的目的是在日本人群中通过CYP 2C 19的聚合酶链反应（PCR）/限制性酶基因分型检查（S）-美芬妥英弱代谢者（PM）表型的可用性。我们对217名无关的健康日本人进行了功能缺陷等位基因CYP 2C 19 m1和CYP 2C 19 m2的基因分型。野生型（wm 1）和CYP 2C 19 m1的频率分别为0.726和0.274，野生型（wm 2）和CYP 2C 19 m2的频率分别为0.892和0.108。虽然观察到的三种基因型的数量非常相似，估计根据Hardy-Weinberg平衡的每一个缺陷，CYP 2C 19 m2未检测到的m1纯合子，和CYP 2C 19 m1未检测到的m2纯合子。在4个家系中分别遗传了两种缺陷，表明CYP 2C 19 m1和m2在同一基因位点上独立分离。在此基础上计算出wm 1-wm 2、CYP 2C 19 m1-wm 2和wm 1-CYP 2C 19 m2的单倍型频率分别为0.618、0.274和0.108。与PM表型相关的CYP 2C 19 m1和CYP 2C 19 m2纯合子和复合杂合子的频率分别为7.5%、1.2%和5.9%。总体而言，14.6%的日本人估计是PM。结果表明，尿S/R比值与PMs检出率（18%）无显著性差异（P > 0.05，chi 2 = 0.545，fd = 1）。我们的数据表明，可以通过基于PCR的CYP 2C 19基因分型鉴定日本（S）-美芬妥英PM。
(S)-Mephenytoin is metabolized by CYP2C19. The purpose of this study was to examine availability of phenotyping of poor metabolizers (PMs) of (S)-mephenytoin by polymerase chain reaction (PCR)/restriction enzyme genotyping of CYP2C19 in a Japanese population. We genotyped 217 unrelated healthy Japanese for functionally defective alleles, CYP2C19m1 and CYP2C19m2. The frequencies of the wild type(wm1) and CYP2C19m1 were 0.726 and 0.274, and the wild type(wm2) and CYP2C19m2 were 0.892 and 0.108 respectively. Although the observed numbers of three genotypes were very similar to those estimated according to the Hardy-Weinberg equilibrium for each defect, CYP2C19m2 was not detected in m1 homozygotes, and CYP2C19m1 was not detected in m2 homozygotes. Two defects were inherited separately in four families indicating CYP2C19m1 and m2 segregate independently at the same gene locus. Based on these data, we calculated the haplotype frequencies of wm1-wm2, CYP2C19m1-wm2 and wm1-CYP2C19m2 to be 0.618, 0.274 and 0.108 respectively. Frequencies of homozygotes for CYP2C19m1 and CYP2C19m2 and compound heterozygotes associated with the PM phenotype, were calculated to be 7.5, 1.2 and 5.9% respectively. In total, 14.6% of Japanese are estimated to be PMs. No significant difference was observed between the frequencies of PMs calculated from our results and that identified by urinary S/R ratio (18%) (p > 0.05, chi 2 = 0.545, fd = 1). Our data indicate that Japanese PMs of (S)-mephenytoin could be identified by PCR-based genotyping of CYP2C19.