Mutation of Fatty Acid Amide Hydrolase in Methamphetamine Abusers

Fatty Acid Amide Hydrolase基因突變在甲基安非他命濫用者的表現

劉興政(Hsing-Cheng Liu) ； 林式榖(Shih-Ku Lin) ； 黃名琪(Ming-Chyi Huang) ； 陳志根(Chih-Ken Chen) ； 吳曉恬(Hsiao-Tein Wu)

《北市醫學雜誌》 3卷1期 (2006/01) Pp. 11-17

https://doi.org/10.6200/TCMJ.2006.3.1.02

摘要

目的：已有許多證據顯示原本存於體內、內因性的cannabinoid系統和成癮行為有關。內因性的cannabinoid會作用於突觸前神經元的CB1受體來調節多巴胺的釋放，進而影響多巴安的成癮求償迴路。Fatty acid amide hydrolase (FAAH) 是體內主要分解內因性脂肪酸胺如anandamide和oleamide的主要酵素。FAAH基因的C385A單一核甘酸多型性變異(single nucleotide polymorphism, SNP)已被報告說和藥物濫用有關。這個SNP會造成FAAH蛋白P129T突變。我們即欲檢測這個SNP和甲基安非他命(methamphetamine, MAP)濫用者的相關性。方法：我們共收案382名MAP濫用者和425位健康對照組。MAP濫用者依其是否出現精神病症狀進一步區分為MAP精神病組和非精神病組。FAAH基因的C385A SNP由PCR-RFLP來檢測。結果：突變AA對偶基因同型出現的頻率在MAP精神病組、MAP飛精神病組和健康對照組分別為0.04、0.02和0.03。AC異型出現的比率分別為0.26、0.31和0.26。結論：本研究並未發現FAAH基因C385A變異和MAP濫用者之間的相關性。

關鍵字

cannabinoid ； fatty acid amide hydrolase ； 甲基安非他命 ； 單一核甘酸多型性變異

並列摘要

Background and Purpose: Compelling evidence has suggested that endogenous cannabinoid system is involved in the addiction disorder. The endocannabinoids would act on presynaptic CB1 receptor to modulate the presynaptic dopamine release in the dopaminergic rewarding pathway. Fatty acid amide hydrolase (FAAH) is the key enzyme in the catalysis of endogenous fatty acid amide such as anandamide and oleamide. FAAH C385A single nucleotide polymorphism (SNP) has been shown to be strongly associated with drug use problem. This SNP would cause P129T missense mutation in FAAH. We tried to examine the association relationship between this SNP and methamphetamine (MAP) abusers. Methods:
382 MAP abusers and 425 healthy normal controls were enrolled in this study. The MAP abusers were further classified into MAP psychosis and non-psychosis groups according to the presence of psychotic symptoms clinically. The FAAH C385A SNP was determined by PCR-RFLP. Results: The distribution of homozygous mutant AA genotype was 0.04 in MAP psychosis, 0.02 in MAP non-psychosis and 0.03 in normal controls. The AC heterozygote in these three clinical groups was 0.26, 0.31 and 0.26, respectively. Conclusion: There was no association between this SNP and MAP abusers in this study in both genotype distribution and allele frequency.

並列關鍵字

cannabinoid ； fatty acid amide hydrolase ； methamphetamine ； single nucleotide polymorphism