CYP2B6型
细胞色素P450
CYP2D6型
羟基化
安非他酮
药理学
内科学
化学
药物遗传学
曲线下面积
微粒体
基因型
内分泌学
医学
新陈代谢
生物化学
CYP3A4型
酶
基因
病理
戒烟
作者
Jidong Lv,Lei Hu,Wei Zhuo,Congmin Zhang,Hong‐Hao Zhou,Fan Li
出处
期刊:Pharmacogenetics and Genomics
[Ovid Technologies (Wolters Kluwer)]
日期:2016-02-01
卷期号:26 (2): 80-87
被引量:16
标识
DOI:10.1097/fpc.0000000000000190
摘要
Background/Aim Cytochrome P450 oxidoreductase (POR) is required for drug metabolism by all microsomal cytochrome P450 (CYP) enzymes. The aim of this study was to investigate whether single-nucleotide polymorphisms in the POR gene were correlated with interindividual variations in CYP2B6 activity, as measured by bupropion hydroxylation. Methods Thirty-five healthy individuals with selected CYP2B6 and POR polymorphisms were involved in the clinical study. The activity of CYP2B6 was evaluated on the basis of the area under the time–concentration curve (AUC) ratio of hydroxybupropion versus bupropion (AUC_hyd/AUC_bup). Results Individuals carrying CYP2B6*1/*1 showed a significantly higher mean AUC_hyd/AUC_bup than individuals carrying the CYP2B6*1/*6 and CYP2B6*6/*6 variants (17.1±6.23 vs. 10.3±4.53, P=0.003 and 17.1±6.23 vs. 9.41±2.84, P=0.002, respectively). POR g.6593A>G (rs2868177) AA homozygotes showed a significantly lower mean AUC_hyd/AUC_bup than POR g.6593A>G AG heterozygotes or GG homozygotes (8.54±2.65 vs. 14.9±6.06, P=0.005 and 8.54±2.65 vs. 16.8±6.45, P=0.002, respectively). Moreover, POR g.6593A>G AA homozygotes had a significantly lower mean AUC_hyd/AUC_bup than the POR g.6593A>G AG/GG genotypes in the CYP2B6*1/*1, CYP2B6*1/*6 and CYP2B6*6/*6 groups (10.9±1.82 vs. 19.7±5.53, P<0.001; 6.18±0.284 vs. 12.1±4.31, P=0.011; and 6.94±1.48 vs. 10.9±2.39, P=0.043, respectively). There was no significant difference in the mean AUC_hyd/AUC_bup among different POR c.1508C>T (*28 or rs1057868) genotypes, even after the effect of CYP2B6*6 was excluded. Conclusion These results indicate, for the first time, that the POR g.6593A>G polymorphism significantly influences CYP2B6 activity, as measured by bupropion hydroxylation, in humans, and the CYP2B6*6 and POR g.6593A>G polymorphisms might be considered simultaneously for the individualized therapy with CYP2B6 substrate drugs such as bupropion.
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