Yang M, Kunugita N, Kitagawa K, Kang S H, Coles B, Kadlubar F F, Katoh T, Matsuno K, Kawamoto T
Department of Environmental Health, University of Occupational and Environmental Health, Kitakyushu 807-8555, Japan.
Cancer Epidemiol Biomarkers Prev. 2001 Jun;10(6):589-93.
Urinary cotinine, one of the main metabolites of nicotine, has been widely used as a biomarker for assessment of direct or passive exposure to cigarette smoke. However, there is wide variation of the cotinine level among smokers who smoke the same number of cigarettes. To use urinary cotinine as a proper exposure-biomarker for cigarette smoke, interindividual variations of cotinine formation must be considered. Therefore, we studied the effects of genetic polymorphisms in drug metabolic enzymes on urinary cotinine levels among 190 male Japanese smokers (ages 19-66 years; mean, 40.6 years). Genetic polymorphisms in cytochrome P-450s (CYP1A1, CYP2A6, CYP2E1), and aldehyde dehydrogenase 2 (ALDH2) were determined by analyzing DNA isolated from peripheral blood. Cotinine in morning spot urine was analyzed by high-performance liquid chromatography. Lifestyle, i.e., smoking, alcohol consumption, and intake of coffee or tea, was examined using a questionnaire. The number of cigarettes smoked and CYP2A6 polymorphism were significantly associated with the urinary cotinine level. Especially, the urinary cotinine levels was drastically lower in CYP2A6-deleted homozygous (CYP2A6*4/4) subjects than in CYP2A61 allele-positive subjects. The polymorphism in the CYP2E1 5'-flanking region was related to the urinary cotinine level in intermediate smokers (who smoke 11-20 cigarettes/day; P < 0.01). Polymorphisms in CYP1A1 or ALDH2, and consumption of alcohol, coffee, or tea were not associated with the urinary cotinine level.
尿可替宁是尼古丁的主要代谢产物之一，已被广泛用作评估直接或被动接触香烟烟雾的生物标志物。然而，吸相同数量香烟的吸烟者之间，可替宁水平存在很大差异。为了将尿可替宁用作香烟烟雾合适的暴露生物标志物，必须考虑可替宁形成的个体间差异。因此，我们研究了药物代谢酶基因多态性对190名日本男性吸烟者（年龄19 - 66岁；平均40.6岁）尿可替宁水平的影响。通过分析从外周血中分离的DNA来确定细胞色素P - 450（CYP1A1、CYP2A6、CYP2E1）和醛脱氢酶2（ALDH2）的基因多态性。采用高效液相色谱法分析晨尿中的可替宁。通过问卷调查了解生活方式，即吸烟、饮酒以及咖啡或茶的摄入量。吸烟数量和CYP2A6基因多态性与尿可替宁水平显著相关。特别是，CYP2A6缺失纯合子（CYP2A6*4/4）受试者的尿可替宁水平比CYP2A61等位基因阳性受试者的尿可替宁水平低得多。CYP2E1 5'侧翼区域的多态性与中度吸烟者（每天吸11 - 20支烟）的尿可替宁水平有关（P < 0.01）。CYP1A1或ALDH2的多态性以及酒精、咖啡或茶的摄入量与尿可替宁水平无关。
