Mynett-Johnson L A, Murphy V E, Claffey E, Shields D C, McKeon P
Department of Genetics, Trinity College, Dublin, Ireland.
Psychiatr Genet. 1998 Winter;8(4):221-5. doi: 10.1097/00041444-199808040-00004.
Catechol-O-methyltransferase (COMT) catalyses the methylation, and hence the inactivation, of catecholamines including the neurotransmitters dopamine and noradrenaline. There is evidence implicating COMT as a candidate gene for a number of neuropsychiatric conditions including bipolar disorder. A long recognized population variation in COMT activity exists and it has recently been established that variation in enzyme activity results from a polymorphic genetic variation within the COMT gene which can be readily assayed as a polymerase chain reaction (PCR)-based restriction fragment length polymorphism (RFLP). A collection of 60 Irish bipolar I probands have been genotyped together with their parents. Tests comparing transmitted and non-transmitted alleles provide no evidence that the polymorphism contributes to a susceptibility to bipolar disorder within the sample as a whole. However, amongst female bipolar I probands (n = 30) there was a tendency for the low-activity allele of COMT to be preferentially transmitted. Furthermore, a re-examination of an Irish case-control sample resulted in a similar observation amongst female bipolar I sufferers and pooling the data sets strengthened the findings.
儿茶酚-O-甲基转移酶（COMT）催化儿茶酚胺（包括神经递质多巴胺和去甲肾上腺素）的甲基化反应，从而使其失活。有证据表明，COMT是包括双相情感障碍在内的多种神经精神疾病的候选基因。COMT活性存在一种长期公认的群体差异，最近已确定酶活性的差异源于COMT基因内的多态性遗传变异，这种变异可以通过基于聚合酶链反应（PCR）的限制性片段长度多态性（RFLP）轻松检测。对60名爱尔兰双相I型先证者及其父母进行了基因分型。比较传递和未传递等位基因的测试没有提供证据表明该多态性在整个样本中导致双相情感障碍易感性。然而，在女性双相I型先证者（n = 30）中，COMT低活性等位基因有优先传递的趋势。此外，对一个爱尔兰病例对照样本的重新检查在女性双相I型患者中得到了类似的观察结果，合并数据集强化了这些发现。
