ALDH2基因多态性与乙醇代谢及外周乙醛积蓄程度的关系

Relationship among ALDH2 Gene Polymorphism,Alcohol Metabolism and Acetaldehyde Level in Peripheral Blood

目的了解不同乙醛脱氢酶2（acetaldehydedehydrogenase2，ALDH2）基因型人群饮酒后，其乙醇药代动力学和外周乙醛积蓄程度。方法收集无血缘关系的志愿者14名，采集静脉血液并且通过聚合酶链反应限制性片段长度多态性技术提取DNA并检测ALDH2基因型，按一定剂量饮酒后，以顶空气相色谱法于不同时间点同时测定血中乙醇及乙醛的含量并计算药代动力学参数。结果根据电泳结果，野生组为5名野生纯合型ALDH2＊1／＊1个体．突变组为9名突变杂合型ALDH2＊1／＊2个体，血中乙醇和乙醛分别在0～1570．7μg/mL和0～5．1772μg／mL范围内线性关系良好。突变组乙醇及乙醛药时曲线下面积（AUC）以及乙醇的末端消除半衰期（tl／2Z）均大于野生组，乙醇的经生物利用度校正的表观消除率（CL／F）小于野生组（P〈0．05）。结论饮酒后，ALDH2＊I／＊2突变组受酶活性抑制影响，血中乙醇和乙醛代谢减慢，造成外周乙醛的蓄积，从而进一步强化其在体内的作用。

Objective To explore alcohol pharmacokinetics as well as acetaldehyde level in penplaeral blood in human subjects with different ALDH2 genotypes after drinking. Methods Venous blood samples of 14 unrelated volunteers were collected. Polymerase chain reaction-restriction fragment length poly morphism technology was adopted for DNA extraction and ALDH2 genotyping. The volunteers were asked to drink beer at certain doses. The concentration of alcohol and acetaldehyde were assayed by headspace gas chromatography method at different time. The pharmacokinetic parameters were calculated. Results According to the results of electrophoresis, 5 people carried ALDH2＊1/＊1 as wild group and 9 people carried ALDH2＊1/＊2 as mutation group. The good linear range of alcohol and acetaldehyde were 0-1 570.7μg/mL and 0-5.1772μg/mL, respectively. The AUC values of alcohol and acetaldehyde and the value of alcohol were higher in the mutation group than that in the wild group. But the CL/F value of alcohol was lower in the mutation group than that in the wild group （P〈0.05）. Conclusion After the consumption of alcohol, alcohol and acetaldehyde metabolism in blood slow down in ALDH2＊1/＊2 muta-ion group influenced by the inhibition of enzyme activity, leading to the accumulation of acetaldehyde in peripheral blood, thus reinforcing their effects in the body.