Human catechol-O-methyltransferase pharmacogenetics: Description of a functional polymorphism and its potential application to neuropsychiatric disorders
Human catechol-O-methyltransferase pharmacogenetics: Description of a functional polymorphism and its potential application to neuropsychiatric disorders
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DOI：
10.1097/00008571-199606000-00007
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发表时间：
1996-06-01
期刊：
影响因子：
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通讯作者：
Weinshilboum, RM
中科院分区：
文献类型：
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作者：
Lachman, HM;Papolos, DF;Weinshilboum, RM
儿茶酚氧位甲基转移酶使儿茶酚胺和邻苯二酚类药物如L多巴失活。人类中一种常见的基因多态与COMT酶活性的三到四个福特变异有关，也与COMT热不稳定的个体变异有关，我们现在证明这是由于G-->；COMT基因第158位密码子的转换导致Valine到蛋氨酸的替代，这两个等位基因可以通过使用限制性内切酶N1a III的基于PCR的限制性片段长度多态分析来识别。识别与酶活性显著变化相关的遗传标记将有助于分析COMT基因在神经精神疾病中的可能作用，在这些疾病中，据信会发生儿茶酚胺神经传递异常，包括情绪障碍、精神分裂症、强迫症、酒精和药物滥用以及注意力缺陷多动障碍。此外，这种多态可能具有药理学意义，因为它将有助于识别表现为儿茶酚类药物代谢异常的患者。
Catechol-O-methyltransferase (COMT) inactivates catecholamines and catechol drugs such as L-DOPA. A common genetic polymorphism in humans is associated with a three-to-four-ford variation in COMT enzyme activity and is also associated with individual variation in COMT thermal instability, We now show that this is due to G-->A transition at codon 158 of the COMT gene that results in a valine to methionine substitution, The two alleles can be identified with a PCR-based restriction fragment length polymorphism analysis using the restriction enzyme N1a III. The identification of a gentic marker associated with significant alterations in enzyme activity will facilitate the analysis of a possible role for the COMT gene in neuropsychiatric conditions in which abnormalities in catecholamine neurotransmission are believed to occur, including mood disorders, schizophrenia, obsessive compulsive disorder, alcohol and substance abuse, and attention deficit hyperactivity disorder, In addition, this polymorphism may have pharmacogentic significance in that it will help make it possible to identify patients who display altered metabolism of catechol drugs.