臺灣博碩士論文加值系統

目的：因過量飲酒會對人體造成傷害，且代謝酒精酵素之基因型的不同會影響酒精代謝的速率，故本研究探討具不同酒精代謝酶基因多形性酒精攝取者，其生物指標變化之情形。
材料與方法：本實驗參考世界衛生組織為篩選酒癮者所設定之
Alcohol Use Disorders Identification Test (AUDIT) 與Cut down,Annoyed, Guilty, Eye-opener (CAGE)問卷，訂定適用於本研究之問卷。經篩選後納入此次實驗共有214 位受試者，其中包括106 位輕度酒精攝取者及108 位重度酒精攝取者。分析項目包括：全套血球分析[white blood count (WBC)、red blood count (RBC)、hemoglobin(Hb) 、mean corpuscular hemoglobin (MCH) 、mean corpuscular hemoglobin concentration (MCHC)、platelet (PLT)及mean corpuscular volume (MCV)] ； 生化分析[Fe 、ferritin 、transferrin (TRF) 、carbohydrate-deficient transferrin (CDT)及CDT/TRF (CDT%)]。另外分析酒精代謝酶[alcohol dehydrogenase 2 (ADH2) 、aldehyde dehydrogenase 2 (ALDH2)、cytochrome P4502E1 (CYP2E1)及catalase (CAT)]基因多形性。
結果：(1) 血液指標之分析：重度酒精攝取者其MCH、MCHC 及MCV
的值均較輕度酒精攝取者為高(p<0.05)；(2) 生化指標之分析：重度酒精攝取者之CDT 與CDT%的值，都較輕度酒精攝取者為高(p<0.05)。(3) 探討具不同酒精代謝酶基因多形性者與飲酒習慣之關係：以ALDH2 wild type 為基準，無論是在allele、genotype [(*1/*2)和(*2/*2)]或phenotype 的分佈上，具有ALDH2 (*1/*1)者較具有ALDH2 *2 攜帶者易成為重度酒精攝取者 (p<0.01)，其餘則無統計學上之差異。(4) 探討結合不同酒精代謝酶基因型者與飲酒習慣之關係：以同時具有ADH2 (*2/*2)與ALDH2 (*1/*2+*2/*2)之酒精攝取者為基準，我們發現：同時具有[ADH2 (*2/*2)與ALDH2 (*1/*1)]及ADH2(*1/*1+*1/*2)與ALDH2 (*1/*1)]之酒精攝取者，均較容易成為重度酒精攝取者 (p<0.001)。此外，以同時具有CYP2E1 (C/T+T/T)與ALDH2 (*1/*2+*2/*2)之酒精攝取者為基準，結果顯示：同時具有[CYP2E1 (C/T+T/T)與ALDH2 (*1/*1)]及[CYP2E1 (C/C)與ALDH2(*1/*1)]之酒精攝取者，均較容易成為重度酒精攝取者 (p<0.001)。最後，以同時具有CAT (C/C)與ALDH2 (*1/*2+*2/*2)之酒精攝取者為基準，結果顯示：同時具有[CAT (C/C)與ALDH2 (*1/*1)]及[CAT(C/T+T/T)與ALDH2 (*1/*1)]之酒精攝取者，均較容易成為重度酒精攝取者 (p<0.01)。(5) 具不同酒精代謝酶基因型組合之酒精攝取者，其生物指標之分析:1 同時具有ADH2 (*2/*2)與ALDH2 (*1/*1)之重度酒精攝取者，其CDT 及CDT%較輕度酒精攝取者為高(p<0.05)。2同時具有ADH2 (*1/*1+*1/*2)與ALDH2 (*1/*1)之重度酒精攝取者，其MCHC 及ferritin 較輕度酒精攝取者為高(p<0.05)。3 同時具有CYP2E1 (C/T+T/T)與ALDH2 (*1/*1) 之重度酒精攝取者，較輕度酒精攝取者無顯著的差異。4 同時具有CYP2E1 (C/C)與ALDH2 (*1/*1) 之重度酒精攝取者，其MCHC 及CDT%較輕度酒精攝取者為高(p<0.05)，而TRF 則較低。5 同時具有CAT (C/C)與ALDH2 (*1/*1) 之重度酒精攝取者，其CDT%較輕度酒精攝取者為高(p<0.05)。○6 同時具有CAT (C/T+T/T)與ALDH2 (*1/*1) 之重度酒精攝取者，則因無統計學上的差異，故沒有討論。
結論：當過量的飲酒時，可能會因其具不同的酒精代謝酶基因型，而有不同的生物指標變化。

Objective: Excessive alcohol intake may cause a lot of damage in tissues,and the rate of alcohol metabolism is affected by various genotypes of alcohol-metabolizing enzymes. Therefore, this study investigated the
changes of biomarkers in the drinkers with various genotypes of alcohol-metabolizing enzymes.
Materials and Methods: We designed an applicable questionnaire for the study, which was adopted from the Alcohol Use Disorders Identification Test (AUDIT) and Cut down, Annoyed, Guilty, Eye-opener (CAGE) questionnaires. 214 participants who were classified according to the questionnaires were enrolled in this study. The participants were divided into two groups that were light drinkers (n = 106) and heavy drinkers (n = 108). The complete blood count (CBC) tests (white blood count [WBC], red blood count [RBC], hemoglobin [Hb], mean corpuscular hemoglobin [MCH], mean corpuscular hemoglobin concentration [MCHC], platelet [PLT] and mean corpuscular volume [MCV]) and the biochemistry tests(Fe, ferritin, transferrin [TRF], carbohydrate-deficient transferrin [CDT], CDT/TRF [CDT%]] were measured. In addition, genotypes of alcohol-metabolizing enzymes, including alcohol dehydrogenase 2 (ADH2), aldehyde dehydrogenase 2
(ALDH2), cytochrome P4502E1 (CYP2E1) and catalase (CAT) were analyzed.
Results: (1) Analysis of hematological markers: There were significantly higher levels of MCH, MCHC and MCV in the heavy drinkers than in the light ones (p<0.05). (2) Analysis of biochemical markers: there were significantly higher levels of CDT and CDT% in the heavy drinkers than
in the light ones (p<0.05). (3) Relationship between the subjects with various genotypes of alcohol-metabolizing enzymes and drinking habits: Those with ALDH2 wild type rather than those with the ALDH2 *2 carrier containing genotype were predisposed to become heavy drinkers,
whatever allele, genotype [(*1/*2) and (*2/*2)], and phenotype (p<0.01), but it did not apply in the subjects with ADH2, CYP2E1 and CAT genotypes. (4) Relationship between the subjects with various combined genotypes of alcohol-metabolizing enzymes and drinking habits: Those with [the ADH2 (*2/*2) and ALDH2 (*1/*1)], and [ADH2
(*1/*1+*1/*2) and ALDH2 (*1/*1)] genotypes rather than those with the ADH2 (*2/*2) and ALDH2 (*1/*1+*1/*2) genotypes were predisposed to become heavy drinkers (p<0.001). In addition, those with [the CYP2E1
(C/T+T/T) and ALDH2 (*1/*1)], and [CYP2E1 (C/C) and ALDH2 (*1/*1)] genotypes rather than those with the CYP2E1 (C/T+T/T) and ALDH2 (*1/*1+*1/*2) genotypes were predisposed to become heavy drinkers (p<0.001). Finally, those with [the CAT (C/C) and ALDH2 (*1/*1)], and
[CAT (C/T+T/T) and ALDH2 (*1/*1)] genotypes rather than those with the CAT (C/C) and ALDH2 (*1/*1+*1/*2) genotypes were predisposed to become heavy drinkers (p<0.01). (5) Changes of biomarkers in the drinkers with various combined genotypes of alcohol-metabolizing enzymes: 1 There were significantly higher levels of CDT and CDT% in
the heavy drinkers with the ADH2 (*2/*2) and ALDH2 (*1/*1) genotypes than in the light drinkers with the same genotypes (p<0.05).2 There were significantly higher levels of MCHC and ferritin in the heavy drinkers with the ADH2 (*1/*1+*1/*2) and ALDH2 (*1/*1) genotypes than in the light drinkers with the same genotypes (p<0.05). 3. There
were no significant biomarker changes in the drinkers with CYP2E1 (C/T+T/T) and ALDH2 (*1/*1) genotypes. ○4 There were significantly higher levels of MCHC and CDT%, and lower levels of TRF in the heavy drinkers with the CYP2E1 (C/C) and ALDH2 (*1/*1) genotypes than in the light drinkers with the same genotypes (p<0.05). 5 There were
significantly higher levels of CDT% in the heavy drinkers with the CAT (C/C) and ALDH2 (*1/*1) genotypes than in the light drinkers with the same genotypes (p<0.05). 6 The number of the participants with the CAT (C/T+T/T) and ALDH2 (*1/*1) genotypes was no significant difference, so the biomarkers were not discussed. Conclusion: Drinkers with various genotypes of alcohol-metabolizing enzymes may demonstrated different biomarker changes when they consume excessive alcohol.

壹 中文摘要 1
貳 英文摘要 4
参 緒論 8
一、文獻回顧 8
二、研究動機與目的 17
三、研究設計 18
肆
第一部分實驗
不同酒精攝取者其生物指標之研究 20
伍
第二部分實驗
不同酒精攝取者其酒精代謝酶基因型之研究 26
陸
第三部份實驗
具不同酒精代謝酶基因型酒精攝取者其生物指標
之研究
43
柒 結論與展望 61
捌 參考文獻 62
玖 圖表 74
壹拾 附錄 108

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