Catechol-O-methyltransferase polymorphisms and schizophrenia: a transmission disequilibrium study in multiply affected families
Catechol-O-methyltransferase polymorphisms and schizophrenia: a transmission disequilibrium study in multiply affected families
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DOI：
10.1097/00041444-199723000-00001
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发表时间：
1997-09-01
影响因子：
0.9
通讯作者：
Collier, DA
中科院分区：
文献类型：
--
作者：
Kunugi, H;Vallada, HP;Collier, DA
儿茶酚-O-甲基转移酶(COMT)代谢多巴胺、去甲肾上腺素和肾上腺素等儿茶酚胺。它在人群中以常见的高活性和低活性等位基因的形式存在(由Valine 158蛋氨酸多态决定)，COMT的高红细胞活性以前曾与精神分裂症有关。为了研究COMT与精神分裂症的遗传关系，采用基于聚合酶链式反应的方法，对22个高加索和日本多病家系进行了传递不平衡检验，其中Val158met和第二个沉默的多态(C256G)。高活性的val158等位基因从父母传递给患病个体的频率高于低活性的met158等位基因，尽管这在统计学上没有显著意义。将这一数据与之前对中国三人家庭精神分裂症的研究(Li等人，1996年)相结合，得出了一个非常有意义的结果(p=0.0015)。G256等位基因也优先传递给受影响的后代，当精神分裂症、分裂情感障碍和未指明的功能性精神病被包括在受影响表型的定义中时，这一点具有统计学意义(p=0.03)。总体而言，这些发现可能表明COMT等位基因对精神分裂症的易感性有影响，或者反映了与附近不同致病基因的连锁不平衡。其他已报道的COMT与强迫症和快速循环型双相情感障碍的关联表明，COMT基因可能对神经精神障碍的易感性和症状具有复杂和多效性的影响。
Catechol-O-methyltransferase (COMT) metabolizes catecholamines such as dopamine, noradrenaline and adrenaline. It exists as common high and low activity alleles in the population (determined by a valine 158 methionine polymorphism), and high red blood cell activity of COMT has previously been associated with schizophrenia. To examine the relationship between COMT and schizophrenia genetically, the transmission disequilibrium test was performed on 22 multiply affected Caucasian and Japanese families genotyped for val158met and a second, silent, polymorphism (C256G), using PCR based assays. The high activity val158 allele was transmitted from parents to the affected individuals more frequently than the low activity met158 allele, although this was not statistically significant. Combining this data with a previous study using Chinese family trios with schizophrenia (Li et al., 1996) gave a highly significant result (p = 0.0015). The G256 allele was also transmitted preferentially to the affected offspring, and this was statistically significant when schizophrenia, schizoaffective disorder and unspecified functional psychosis were included in the definition of the affected phenotype (p = 0.03). Overall, these findings may indicate an effect of COMT alleles on susceptibility to schizophrenia, or reflect linkage disequilibrium with a different causative polymorphism in the vicinity. Other reported associations of COMT with obsessive compulsive and rapid cycling bipolar disorder indicate that the COMT gene may have complex and pleiotropic effects on susceptibility and symptomatology of neuropsychiatric disorders.