Koonrungsesomboon Nut, Khatsri Rapheephorn, Wongchompoo Penwisa, Teekachunhatean Supanimit
Department of Pharmacology, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand.
Pharmacogenomics J. 2018 Dec;18(6):760-768. doi: 10.1038/s41397-017-0011-3. Epub 2017 Dec 27.
A large interindividual variation in the activity of cytochrome P450 1A2 (CYP1A2) raises concern about therapeutic failure or toxicity when medical professionals prescribe drugs extensively metabolized by CYP1A2. To date, a number of studies have assessed the association between genetic polymorphisms and CYP1A2 activity; however, there are controversies as to the functional importance of CYP1A2 polymorphisms on the metabolism of CYP1A2 substrates. This systematic review and meta-analysis assessed the effects of genetic polymorphisms on CYP1A2 activity, as measured by caffeine metabolism, in a total of 3570 individual subjects. Higher enzyme activity was observed among those who were homozygous or heterozygous for the -163C>A polymorphism (rs762551), when compared to the wild-type individuals (SMD = 0.40, 95%CI = 0.12-0.68, p = 0.005; SMD = 0.32, 95%CI = 0.11-0.54, p = 0.003, respectively) and this was more pronounced among smokers (SMD = 0.92, 95%CI = 0.27-1.57, p = 0.005; SMD = 0.56, 95%CI = 0.22-0.90, p = 0.001, respectively). For other CYP1A2 polymorphisms, altered caffeine metabolic ratios were not seen. Our results indicate the functional importance of -163C>A polymorphism on CYP1A2 inducibility in humans.
细胞色素P450 1A2（CYP1A2）活性存在较大个体差异，这使得医学专业人员在开具经CYP1A2广泛代谢的药物时，担心会出现治疗失败或毒性问题。迄今为止，已有多项研究评估了基因多态性与CYP1A2活性之间的关联；然而，关于CYP1A2多态性对CYP1A2底物代谢的功能重要性仍存在争议。本系统评价和荟萃分析评估了基因多态性对总共3570名个体受试者中通过咖啡因代谢测定的CYP1A2活性的影响。与野生型个体相比，-163C>A多态性（rs762551）纯合或杂合的个体中观察到较高的酶活性（标准化均数差分别为0.40，95%置信区间为0.12 - 0.68，p = 0.005；标准化均数差为0.32，95%置信区间为0.
