臺灣博碩士論文加值系統

研究背景
酒癮是一個複雜又具高度遺傳性的精神疾病。血清素接受體1B(5HT1B)基因被認為是酒癮的候選致病基因。由於酒癮是一個具有高度異質性的疾病，在遺傳學的探討上，適當的亞型區分亦相當重要。本研究擬探討在不同酒癮亞型分類下，5HT1B基因與酒癮的關係。另外，5HT1B基因被認為與焦慮症、憂鬱症、反社會人格的病理機制相關，焦慮憂鬱症與反社會性人格疾患及酒癮又有很高的共病率，本研究擬進一步探討5HT1B基因與焦慮憂鬱型酒癮與反社會型酒癮間的基因關聯性，以釐清這兩種常共病但卻有不同臨床表現的酒癮亞型間的基因關係。
研究方法
本研究為橫斷面研究，採個案對照研究設計，一共收集522位漢族個案，其中包括322位酒癮患者及200位正常控制組。酒癮組根據DSM-IV診斷標準分為單純型酒癮、焦慮憂鬱型酒癮、酒癮合併反社會人格違常等三種亞型。對個案進行抽血及DNA的萃取，以實驗室方式區分5HT1B(A-161T)基因多型性的基因型態，進行統計分析。
結果
在5HT1B(A-161T)基因多型性的基因型(genotype)或對偶基因頻率(allele frequency)的分布上，酒癮組及各個酒癮亞型組與正常控制組間並無顯著差異。然而，不論在genotype或allele frequency的分布上，焦慮憂鬱型酒癮與酒癮合併反社會人格違常兩種亞型間皆出現顯著差異。
結論
5HT1B(A-161T)基因多型性並非是酒癮或其亞型的候選基因。然而，5HT1B(A-161T)基因多型性可能與分辨焦慮憂鬱型酒癮與酒癮合併反社會人格違常的病因有關。

Background: Several studies have suggested that the serotonin receptor 1B gene (5HT1B) may be important in the pathogenesis of alcohol dependence (alcoholism; ALC; AD). We examined whether 5HT1B gene A-161T polymorphisms (rs130058) is a susceptibility factor for total AD and subgroups of AD. We further explored correlation of this 5HT1B gene variant between anxiety-depression alcoholism and antisocial alcoholism subgroups because of the high comorbidity of anxiety-depression, antisocial personality disorder, and AD.
Methods: We recruited 522 Han Chinese in Taiwan for this study: 322 AD patients and 200 controls. The patient group was recruited primarily from medical teaching hospitals; patients with antisocial alcoholism were recruited from Taiwanese prisons. Individuals with AD were classified into three homogeneous clinical subgroups—Pure Alcoholism (Pure ALC), Anxiety-Depression Alcoholism (ANX/DEP ALC) and Antisocial Alcoholism (Antisocial ALC)—using DSM-IV diagnosis. The 5HT1B gene A-161T polymorphism was determined by PCR-RFLP.
Results: No significant differences in genotypic and allelic frequencies were found between controls and the total AD group nor between controls and the three AD subgroups. However, there were significant difference in the 5HT1B gene A-161T polymorphism at both the genotype and allelic levels between the ANX/DEP ALC and Antisocial ALC subgroups.
Conclusions: This study suggests that the 5HT1B gene A-161T polymorphism alone is not a risk factor for increasing susceptibility to either AD or its subtypes. However, 5HT1B gene A-161T polymorphisms in might be one of the common genetic factors between the ANX/DEP ALC and Antisocial ALC subgroups.

Abstract in Chinese……………………………………………iii
Abstract…………………………………………………………iv.
Acknowledgment………………………………………………v
Table of Contents………………………………………………vi
List of Tables……………………………………………………vii
1. Introduction
1.1 Alcohol Dependence……………………………………1
1.2 Alcohol Dependence and genes………………………2
1.3 Alcohol Dependence and Serotonin System……………3
1.4 5-HT1B receptor and alcohol dependence……………5
1.5 Subtypes of Alcohol Dependence………………………7
1.6 Positive correlation between antisocial personality disorder and anxiety disorder…………………………9
1.7 Aim……………………………………………………10
2. Materials and Methods
2.1 Subjects…………………………………………………11
2.2 Clinical Measures………………………………………14
2.3 Blood samples and DNA extraction……………………15
2.4 Genotyping of 5HT1B genes…………………………16
2.5 Statistical Analysis……………………………………18
3. Results
3.1 Demographic data………………………………………19
3.2 Genotype distributions…………………………………20
4. Discussion
4.1 Association of the 5HT1B gene (A-161T polymorphisms) with AD………………………………21
4.2 Association of the 5HT1B gene (A-161T polymorphisms) between with ANX/DEP ALC and Antisocial ALC subgroups……………………………22
4.3 Limitations……………………………………………25
5. Conclusion…………………………………………………27
6. Reference……………………………………………………28
7. Tables………………………………………………………39
8. Appendix……………………………………………………42

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