Lachman H M, Papolos D F, Saito T, Yu Y M, Szumlanski C L, Weinshilboum R M
Department of Medicine, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Pharmacogenetics. 1996 Jun;6(3):243-50. doi: 10.1097/00008571-199606000-00007.
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-fold 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 Nla 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 pharmacogenetic significance in that it will help make it possible to identify patients who display altered metabolism of catechol drugs.
儿茶酚-O-甲基转移酶（COMT）可使儿茶酚胺和儿茶酚类药物（如左旋多巴）失活。人类中一种常见的基因多态性与COMT酶活性三到四倍的变化相关，也与COMT热稳定性的个体差异有关。我们现在表明，这是由于COMT基因第158位密码子发生G→A转换，导致缬氨酸被甲硫氨酸取代。使用限制性内切酶Nla III，通过基于聚合酶链反应（PCR）的限制性片段长度多态性分析可识别这两个等位基因。鉴定与酶活性显著改变相关的基因标记，将有助于分析COMT基因在儿茶酚胺神经传递异常被认为会发生的神经精神疾病中的可能作用，这些疾病包括情绪障碍、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，这种多态性可能具有药物遗传学意义，因为它将有助于识别儿茶酚类药物代谢改变的患者。
