- 作者: 魯思翁; 王明芳; 林棟樑; 高茂涵; 陳美玲; 江樵熹; 白璐; 尹士俊
- 作者服務機構: 三軍總醫院精神醫學部; 國防醫學院生化學科; 國防醫學院藥學系; 國防部醫學院公共衛生學系; 法務部調查局
- 中文摘要:
醇脫氫?(ADH)和醛脫氫?(ALDH)是人類主要之酒精代謝?。此二?在不同種族均有遺傳多型性。約半數國人缺
失粒線體ALDH2之活性,而此失活被認為是酒癮之負危險生物因子。為研究不同ALDH2基因型國人之乙醇及乙醛代
謝,我們應用聚合?連鎖反應導向突變及限制?切斷片長度多型性測定273位男性成年人的ADH2, ADH3, ALDH2對偶
基因型。在143位ADH2*2及ADH3*1均為同型接合子者中,ALDH2*1/*1, ALDH2*1/*2, ALDH2*2/2基因型者分別
為80,55,8位。在此三組中各選5位做酒精排除之測試。於飲低劑量乙醇(0.2克/公斤體重)後,在130分鐘內之不同時
問分別應用氣相層析及高壓液相層析測定其血中乙醇及乙醛之濃度。ALDH2*2/2突變同型接合子和異型接合子者之乙
醛峰濃度及其血中濃度對時閒曲線下之面積(AUC)均較ALDH2*1/*1正常同型接合子者顯著為高,其中又以突變同型接
合子者為最高。突變同型接合子者之血中乙醇峰濃度及其AUC均較正常同型接合子者顯著為高。在所測試之17項主觀
感覺中,心跳加快,臉部發熱,受酒精影響及頭暈等四項酒精反應對突變同型接合子者為最明顯。我們的結果顯示,拒
酒基因ALDH2*2所以會保護國人不發生酒癮,在於即使飲用低劑量酒精,其能造成血中乙醛濃度顯著升高並因之而產
生不舒服之生理反應。
名 - 英文摘要: Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) are the major enzymes respon- sible for ethanol metabolism in humans. Both enzymes exhibit genetic polymorphisms among racial popula- tions. About half of the Chinese population lack mitochondrial ALDH2 activity and such a deficiency has been believed to be a negative risk factor for the development of alcoholism. To assess ethanol and acetaldehyde metabolism in Chinese with different ALDH2 genotypes, we genotyped 273 male adults at the ADH2, ADH3, and ALDH2 loci by using polymerase chain reaction-directed mutagenesis and restriction fragment length polymorphisms. Of the 143 individuals homozygous for both the ADH2*2 and the ADH3*1 alleles, 80, 55, and 8 were identified as ALDH2*1/*1, ALDH2*1/*2, and ALDH2*2/*2, respectively. Five each from the above three ALDH2 genotypic subjects underwent alcohol elimination testing. Blood ethanol and acetaldehyde levels were determined at various times up to 130 min after intaking a low dose of ethanol (0.2 g/kg body weight) by using head-space gas chromatography and high-performance liquid chromato- graphy with fluorescence detection, respectively. The mutant homozygotes of ALDH2*2/*2 and the hetero- zygotes exhibited significantly higher peak acetaldehyde concentrations and also greater areas under the blood concentrations-time curve (AUC) than did the normal homozygotes of ALDH2*1/*1, with the mutant homozygotes both being the largest. The mutant homozygotes displayed significantly higher peak ethanol levels and AUC compared to the normal homozygotes. Of the 17 subjective feeling items tested, palpitation, facial warming, effects of alcohol, and dizziness were found to be most pronounced among the mutant homozygotes. In conclusion, our results support the theory that the alcohol-rejecting gene of ALDH2*2 exerts its protection against alcoholism by elevating blood acetaldehyde levels after a low dose of alcohol and through the associated discomfort physiological responses.
- 中文關鍵字: aldehyde dehydrogenase-2; genotype; ethanol; acetaldehyde; metabolism.
- 英文關鍵字: --