Li-Chen Gao1, Fang-Qun Liu2, Li Yang3, Lin Cheng4, Hai-Ying Dai5, Ran Tao5, Shi-Peng Cao6, Di Wang7, Jie Tang8. 1. Department of Pharmacy, Changsha Central Hospital, Changsha, 410004, Hunan, People's Republic of China. gonedog1224@hotmail.com. 2. Department of Pharmacy, Changsha Central Hospital, Changsha, 410004, Hunan, People's Republic of China. 3. Department of Pharmacy, Changsha Central Hospital, Changsha, 410004, Hunan, People's Republic of China. yl7618@126.com. 4. State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, 510060, Guangdong, People's Republic of China. 5. Department of Cardiology, Changsha Central Hospital, Changsha, 410004, Hunan, People's Republic of China. 6. Tuberculosis Research Center, Pulmonary Hospital, Changsha Central Hospital, Changsha, 410004, Hunan, People's Republic of China. 7. Department of Oncology, Cancer Institute, Changsha Central Hospital, Changsha, 410004, Hunan, People's Republic of China. 8. Institute of Clinical Pharmacology, Central South University, Changsha, 410078, Hunan, People's Republic of China.
Abstract
AIM: To investigate whether single-nucleotide polymorphisms (SNPs) in the P450 oxidoreductase (POR) gene were correlated with interindividual variations in cytochrome P450 (CYP) 2B6 activity. METHODS: Thirty-six healthy volunteers who tested CYP2B6 and POR polymorphisms were enrolled in the study. CYP2B6 activity was measured by bupropion hydroxylation with LC/MS/MS. The ratio of hydroxybupropion versus bupropion (AUC_hyd/AUC_bup) in terms of area under the time-concentration curve (AUC) was used to represent the CYP2B6 activity. RESULTS: The volunteers carrying CYP2B6*1/*1 showed a significantly higher mean AUC_hyd/ AUC_bup than those CYP2B6*1/*6 and CYP2B6*6/*6 variants (15.66 ± 1.65 vs. 9.25 ± 1.92, P = 0.008 and 15.66 ± 1.65 vs. 8.21 ± 1.74, P = 0.006, respectively). POR rs2868177 (6593 A > G) AA homozygotes showed a significantly lower mean AUC_hyd/ AUC_bup than that of POR rs2868177 AG heterozygotes or GG homozygotes (8.13 ± 1.37 vs. 12.15 ± 2.97, P = 0.005 and 8.13 ± 1.37 vs. 17.59 ± 3.25, P = 0.001, respectively). Moreover, POR rs2868177 AG heterozygotes and GG homozygotes showed a significantly increased mean AUC_hyd/AUC_bup than AA homozygotes in the CYP2B6*1/*1 and CYP2B6*6 carriers (16.40 ± 2.01 vs. 12.40 ± 1.45, P = 0.006 and 10.65 ± 1.47 vs. 6.54 ± 1.25, P = 0.004, respectively). Meanwhile, a strong correlation between the genetic variations (POR rs2868177 and CYP2B6*6) and AUC_hyd/ AUC_bup was found (P = 0.009 and P = 0.001, respectively). There was no significant difference in the mean AUC_hyd/AUC_bup among different POR *28 genotypes (P > 0.05). CONCLUSION: POR rs2868177 and CYP2B6*6 variants contribute to the interindividual variability in human CYP2B6 activity, which may affect the disposition and interaction of other CYP2B6 substrate drugs.
AIM: To investigate whether single-nucleotide polymorphisms (SNPs) in the P450 oxidoreductase (POR) gene were correlated with interindividual variations in cytochrome P450 (CYP) 2B6 activity. METHODS: Thirty-six healthy volunteers who tested CYP2B6 and POR polymorphisms were enrolled in the study. CYP2B6 activity was measured by bupropion hydroxylation with LC/MS/MS. The ratio of hydroxybupropion versus bupropion (AUC_hyd/AUC_bup) in terms of area under the time-concentration curve (AUC) was used to represent the CYP2B6 activity. RESULTS: The volunteers carrying CYP2B6*1/*1 showed a significantly higher mean AUC_hyd/ AUC_bup than those CYP2B6*1/*6 and CYP2B6*6/*6 variants (15.66 ± 1.65 vs. 9.25 ± 1.92, P = 0.008 and 15.66 ± 1.65 vs. 8.21 ± 1.74, P = 0.006, respectively). PORrs2868177 (6593 A > G) AA homozygotes showed a significantly lower mean AUC_hyd/ AUC_bup than that of PORrs2868177 AG heterozygotes or GG homozygotes (8.13 ± 1.37 vs. 12.15 ± 2.97, P = 0.005 and 8.13 ± 1.37 vs. 17.59 ± 3.25, P = 0.001, respectively). Moreover, PORrs2868177 AG heterozygotes and GG homozygotes showed a significantly increased mean AUC_hyd/AUC_bup than AA homozygotes in the CYP2B6*1/*1 and CYP2B6*6 carriers (16.40 ± 2.01 vs. 12.40 ± 1.45, P = 0.006 and 10.65 ± 1.47 vs. 6.54 ± 1.25, P = 0.004, respectively). Meanwhile, a strong correlation between the genetic variations (PORrs2868177 and CYP2B6*6) and AUC_hyd/ AUC_bup was found (P = 0.009 and P = 0.001, respectively). There was no significant difference in the mean AUC_hyd/AUC_bup among different POR *28 genotypes (P > 0.05). CONCLUSION:PORrs2868177 and CYP2B6*6 variants contribute to the interindividual variability in humanCYP2B6 activity, which may affect the disposition and interaction of other CYP2B6 substrate drugs.
Authors: Haoming Zhang; Chitra Sridar; Cesar Kenaan; Hemali Amunugama; David P Ballou; Paul F Hollenberg Journal: J Pharmacol Exp Ther Date: 2011-06-09 Impact factor: 4.030
Authors: F Haroun; L Al-Shaar; R H Habib; N El-Saghir; A Tfayli; A Bazarbachi; Z Salem; A Shamseddine; A Taher; I Cascorbi; N K Zgheib Journal: Cancer Chemother Pharmacol Date: 2014-11-27 Impact factor: 3.333
Authors: Ana M Gomes; Stefan Winter; Kathrin Klein; Miia Turpeinen; Elke Schaeffeler; Matthias Schwab; Ulrich M Zanger Journal: Pharmacogenomics Date: 2009-04 Impact factor: 2.533
Authors: Marianne Rodrigues Fernandes; Juliana Carla Gomes Rodrigues; Olalla Maroñas; Ana Latorre-Pellicer; Raquel Cruz; João Farias Guerreiro; Rommel Mario Rodriguez Burbano; Paulo Pimentel de Assumpção; Andrea Ribeiro-Dos-Santos; Sidney Emanuel Batista Dos Santos; Angel Carracedo; Ney Pereira Carneiro Dos Santos Journal: Pharmgenomics Pers Med Date: 2021-01-22