Obase Yasushi, Shimoda Terufumi, Kawano Tetsuya, Saeki Sachiko, Tomari Shin-Ya, Mitsuta-Izaki Kazuko, Matsuse Hiroto, Kinoshita Moritoshi, Kohno Shigeru
Second Department of Internal Medicine, Nagasaki University School of Medicine, Nagasaki, Japan.
Clin Pharmacol Ther. 2003 May;73(5):468-74. doi: 10.1016/s0009-9236(03)00013-4.
Cytochrome p450 (CYP) 1A2 gene polymorphisms are thought to be involved in theophylline metabolism.
We analyzed the effect of genetic polymorphisms in the 5'-flanking region to the first intron of the CYP1A2 gene on theophylline metabolism in 75 Japanese patients with asthma and 159 healthy Japanese volunteers.
Genetic polymorphisms were detected at 4 sites of the CYP1A2 gene, -2964(G/A) and -1569(T/del) in the 5'-flanking region and 155(T/G) and 731(A/C) in the first intron.
There were no significant differences in the distribution of gene polymorphisms between the asthmatic and control groups. Among asthmatic patients, theophylline clearance was significantly lower in patients with the polymorphism at site -2964(G/A) whose genotype was G/A (0.029 +/- 0.001 L x h(-1) x kg(-1)) or A/A (0.029 +/- 0.002 L x h(-1) x kg(-1)) than in those whose genotype was G/G (0.034 +/- 0.001 L x h(-1) x kg(-1)) (P <.01 and P <.05, respectively). High theophylline clearance levels significantly correlated with age in the G/G subgroup of site -2964(G/A) (P <.05, r = -0.35) but not in the G/A or A/A subgroup.
Given its potential side effects, theophylline may need to be used with care in patients with the A allele at site -2964(G/A) in the CYP1A2 gene, because theophylline metabolism levels are lower in such patients, particularly in young asthmatic individuals.
细胞色素P450（CYP）1A2基因多态性被认为与茶碱代谢有关。
我们分析了CYP1A2基因5'侧翼区至第一内含子的基因多态性对75例日本哮喘患者和159例健康日本志愿者茶碱代谢的影响。
在CYP1A2基因的4个位点检测基因多态性，5'侧翼区的-2964（G/A）和-1569（T/del）以及第一内含子的155（T/G）和731（A/C）。
哮喘组和对照组之间基因多态性的分布没有显著差异。在哮喘患者中，-2964（G/A）位点基因型为G/A（0.029±0.001L×h-1×kg-1）或A/A（0.029±0.002L×h-1×kg-1）的患者茶碱清除率显著低于基因型为G/G（0.034±0.001L×h-1×kg-1）的患者（分别为P<.01和P<.05）。-2964（G/A）位点G/G亚组中，高茶碱清除率水平与年龄显著相关（P<.05，r=-0.35），但在G/A或A/A亚组中则不然。
鉴于其潜在的副作用，对于CYP1A2基因-2964（G/A）位点携带A等位基因的患者，使用茶碱时可能需要谨慎，因为此类患者的茶碱代谢水平较低，尤其是年轻哮喘患者。
