Unit of Pharmacogenetics and Clinical Psychopharmacology, Centre for Psychiatric Neurosciences, Department of Psychiatry, CHUV, University of Lausanne, Hospital of Cery, Prilly, Switzerland.
Clin Pharmacol Ther. 2011 Jul;90(1):117-25. doi: 10.1038/clpt.2011.70. Epub 2011 May 18.
Cytochrome P4501A2 (CYP1A2) is involved in the metabolism of several drugs and is induced by smoking. We aimed to determine the interindividual change in CYP1A2 activity after smoking cessation and to relate it to CYP1A2 genetic polymorphisms. CYP1A2 activity was determined from the paraxanthine:caffeine ratio in 194 smokers and in 118 of them who had abstained from smoking during a 4-week period. The participants were genotyped for CYP1A21F, 1D, and 1C polymorphisms. Smokers had 1.55-fold higher CYP1A2 activity than nonsmokers (P < 0.0001). The individual change in CYP1A2 activity after smoking cessation ranged from 1.0-fold (no change) to a 7.3-fold decrease in activity. In five participants with low initial CYP1A2 activity, an increase was observed after smoking cessation. Before smoking cessation, the following factors were found to influence CYP1A2 activity: CYP1A21F (P = 0.005), CYP1A21D (P = 0.014), the number of cigarettes/day (P = 0.012), the use of contraceptives (P < 0.001), and -163A/-2467T/-3860G haplotype (P = 0.002). After quitting smoking, only CYP1A21F (P = 0.017) and the use of contraceptives (P = 0.05) had an influence. No influence of CYP1A2 polymorphisms on the inducibility of CYP1A2 was observed.
细胞色素 P4501A2（CYP1A2）参与多种药物的代谢，并且可被吸烟诱导。我们旨在确定戒烟后 CYP1A2 活性的个体变化，并将其与 CYP1A2 遗传多态性相关联。在 194 名吸烟者和其中 118 名在 4 周期间戒烟的吸烟者中，通过对茶碱：咖啡因比值来确定 CYP1A2 活性。参与者进行了 CYP1A21F、1D 和1C 多态性的基因分型。吸烟者的 CYP1A2 活性比不吸烟者高 1.55 倍（P < 0.0001）。戒烟后 CYP1A2 活性的个体变化范围从 1.0 倍（无变化）到活性降低 7.3 倍。在 5 名初始 CYP1A2 活性较低的参与者中，戒烟后观察到活性增加。在戒烟前，以下因素被发现影响 CYP1A2 活性：CYP1A21F（P = 0.005）、CYP1A21D（P = 0.014）、每天吸烟的支数（P = 0.012）、使用避孕药（P < 0.001）和-163A/-2467T/-3860G 单倍型（P = 0.002）。戒烟后，只有 CYP1A21F（P = 0.017）和使用避孕药（P = 0.05）有影响。未观察到 CYP1A2 多态性对 CYP1A2 诱导性的影响。
