海洛因成癮者之單胺氧化酶A基因啟動子多形性與反社會性人格傾向無關

背景: 隨著國內經濟成長、政治及社會變遷，近來毒品濫用盛行。台灣九十四年一月間，因毒品而裁判有罪確定之人數較去年同期成長了84.6 %，一級毒品部分人數則更增長96.6%。在2004年Gerra G 等之研究中，分析199位義大利後裔男性，其中95位健康人、以及104位海洛因依賴者(含52位併有暴力行為與反社會性人格疾患)的MAOA promoter gene 多形性，低活性的3-repeat allele出現頻率在併有暴力之海洛因依賴者明顯較高，但沒有反社會性行為海洛因依賴者(34.6 vs. 15.4%; p<0.03)與控制組(18.9%; p<0.05)較低。各種MAOA gene promoter 之long-allele 或 short-allele的出現頻率在海洛因依賴組與控制組並無統計上的差別，高活性的4-repeat allele出現頻率於無反社會性行為的海洛因依賴者比有反社會性行為的海洛因依賴者來得高(76.9 vs. 55.8%; p<0.02)。目的: 本研究擬探究男性華人之海洛因成癮者(heroin addicts)與隨機取樣之社區組之X染色體單胺氧化酶A基因啟動子多形性(MAOA gene promoter polymorphism)基因型分佈，並進一步分析在海洛因成癮者中，反社會性人格傾向及X染色體單胺氧化酶A基因啟動子多形性(MAOA gene promoter polymorphism)的潛在相關性。方法: 本研究收集符合SCID for DSM-III-R之海洛因依賴診斷標準者為個案組544位，以隨機抽樣之台灣台南某社區男性個案184位為對照組。反社會性人格傾向則以犯罪行為之「任何前科紀錄之有無」、「毒品前科紀錄之有無」、「非毒品之其他前科紀錄之有無」、及「暴力攻擊前科之有無」來評估。結果: 研究結果顯示MAOA gene promoter 多形性與海洛因依賴個案並無相關性，也與反社會性人格傾向無相關性。經過迴歸分析發現，「教育程度低(≦9 年)」、及「父母婚姻異常」與「有任何前科紀錄」有相關，但MAOA gene promoter則無相關；亦即教育程度低、及父母婚姻異常可預測「反社會人格傾向」，但是MAOA gene promoter不能預測「反社會人格傾向」。結論: 我們研究發現建議MAOA gene promoter多形性在男性華人的海洛因依賴並無主要之調節角色，但不能排除MAOA gene 其他的位置之多形性會影響到海洛因依賴出現。未來的海洛因依賴研究上，有必要進一步探索MAOA gene其他位置之多形性、不同神經傳導物質系統之多形性的交互影響、以及基因型與環境交互影響(Genome - Environment Interaction)。

關鍵字

海洛因成癮者；毒品濫用；海洛因依賴；基因型與環境交互影響；反社會人格傾向；單胺氧化?A基因啟動子多形性；前科紀錄

並列摘要

Background: Following the trend of domestic economic growth, political, and society's changes, narcotics abuse become common in Taiwan recently. In January 2005, the number of drugs abuse criminals being sentenced guilty grow up 84.6%, as compared with January 2004. In the same period of last year relatively, first class drugs crimes increases by 96.6%. In Gerra et al. study, the repeat number of the MAOA functional polymorphism was assessed in 199 male subjects of Italian descent, a sample comprising 95 healthy subjects and 104 heroin-dependent subjects including 52 addicted individuals with violent behaviour and antisocial personality disorder demonstrated that the frequency of the low-activity 3-repeat allele was significantly higher in violent offenders among heroin addicts, compared to addicted individuals without antisocial behaviour (34.6 vs. 15.4%; p<0.03) and controls (18.9%; p<0.05). No significant difference was evidenced in the frequencies of the MAOA alleles between heroin-dependent subjects in general and control subjects. High activity 4-repeat allele frequency was significantly higher in addicted individuals without antisocial behavior compared to antisocial-aggressive heroin-dependent subjects (76.9 vs. 55.8%; p<0.02). Aims: We planed to explore the alleles distribution of the MAOA gene promoter polymorphism in Chinese male with heroin addiction and a random-selected community group. Furthermore, we analyzed the potential association between MAOA gene promoter polymorphism and antisocial personality traits in heroin addicts. Methods: The repeat number (3–5) of the MAOA-uVNTR functional polymorphism was determined in 544 male heroin dependence subjects according to SCID for DSM-III-R and 184 random-selected community male controls from Tainan, Taiwan. Antisocial personality traits were evaluated by the criminal behaviors, such as any criminal records, illegal substance abuse criminal records, other criminal records except illegal substance abuse, and violence-aggressive criminal records. Results: These results demonstrated that there are no association between MAOA gene promoter polymorphism and heroin dependence, and no association between MAOA gene promoter polymorphism and antisocial personality traits. With logistic regression, low level of education, parent’s abnormal marriage statuses, but not MAOA gene promoter polymorphism, are correlated with subjects with criminal records. Low level of education (≦9 years) and parent’s abnormal marriage status, but not MAOA gene promoter polymorphism, can predict antisocial personality traits. Conclusion: Our findings suggest that MAOA gene promoter polymorphism does not play a major role in the modulation of heroin dependence in Chinese males, but we could not exclude that other polymorphisms of the MAOA gene affect heroin dependence. Further exploration of the other polymorphisms of the MAOA gene, multiple interactions of polymorphisms in various neurotransmitters systems, genome-environment interactions may be needed in future studies of heroin dependence.

並列關鍵字

narcotics addiction ； heroin dependence ； heroin addicts ； antisocial personality traits ； MAOA gene promoter polymorphism ； criminal records ； genome-environment interactions