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題名 | 淺談FAAH (rs324420)藥物基因體學=Discussion on Pharmacogenetic Researches of Fatty Acid Amide Hydrolase |
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作 者 | 廖顯鋒; 阮盈萍; 潘俊旭; | 書刊名 | 藥學雜誌 |
卷期 | 35:3=140 2019.09[民108.09] |
頁次 | 頁40-45 |
分類號 | 418.1 |
關鍵詞 | 脂肪酸醯胺水解酶; 藥物成癮; 單核苷酸多型性; Fatty acid amide hydrolase; Drug addition; Single nucleotide polymorphisms; |
語文 | 中文(Chinese) |
中文摘要 | 脂肪酸醯胺水解酶 (FAAH) 位於1號染色體上1p33的基因,為編碼579個氨基酸的 跨膜結構;在這基因中發現的幾個突變所導致 mRNA 穩定性和轉錄速率改變或編碼 蛋白質的活性降低。有較多的證據表示這些功能突變與古柯鹼,酒精,大麻,海洛 因,尼古丁依賴性以及其他藥物生理有關,其中影響最明顯的是 FAAH 385C > A SNP (rs324420) 單核苷酸多型性 (SNP),且這種基因多型性導致 FAAH 胺基酸序列上位置 129上的脯胺酸 (proline) 被蘇胺酸 (threonine) 取代,而這種取代在模擬結構上的差異也 可能造成 FAAH 本身更容易受到蛋白水解酶降解,因此未來在藥物成癮和其他精神疾 病藥物治療研究上扮演重要的角色。 |
英文摘要 | The fatty acid amide hydrolase (FAAH) genes are located on chromosomes 1 in the 1p33 cytogenetic bands, and FAAH encodes the transmembrane domain of 579 amino acids. Several mutations found in the gene lead to altered mRNA stability and transcription rate or a decrease on the activity of the encoded protein. Recently, there has been more evidence to show that these functional mutations are related to the dependence upon cocaine, alcohol, marijuana, heroin, nicotine and other drugs. One of the most compelling associations is with the C385A single nucleotide polymorphism (SNP), which is found in the FAAH gene. Moreover, many works have repeatedly associated polymorphisms in the FAAH 385C > A SNP (rs324420) with drug-related behaviors, which may alter the protein functional structure in molecular simulation analysis by substituting the threonine for the proline in the 129 site. It was suggested that this SNP should be examined in further genetic studies focusing on drug addiction and other psychiatric disorders. |
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