De Luca Vincenzo, Voineskos Sophocles, Wong Greg, Kennedy James L
Neurogenetics Section, Clarke Site, Centre for Addiction and Mental Health, Department of Psychiatry, University of Toronto, 250 College Street R-30, Toronto, ON, Canada, M5T 1R8.
Exp Brain Res. 2006 Sep;174(2):292-6. doi: 10.1007/s00221-006-0458-y. Epub 2006 Apr 25.
Cholinergic dysfunction is one of the hypotheses for the cognitive deficits of schizophrenia. Neurocognitive deficits, which are well-described clinical features of schizophrenia, may be remediated by nicotine; therefore investigations of nicotinic receptor subtypes is of considerable clinical interest. We typed polymorphisms in CHRNA4 and CHRNB2 genes controlling the expression of neuronal high-affinity nicotinic receptors in 117 Canadian families having at least one schizophrenic patient. Using a family-based association strategy, we performed allele, haplotype and interaction analysis of these two loci. In the families tested, the two cholinergic genes interact to affect schizophrenia in combination (P=0.010), while neither was sufficient alone to confer susceptibility. Our present study provided the first line of direct evidence suggesting that the CHRNA4 gene combined with CHRNB2 receptor gene may be linked to schizophrenia.
胆碱能功能障碍是精神分裂症认知缺陷的假说之一。神经认知缺陷是精神分裂症已被充分描述的临床特征，可能会被尼古丁改善；因此，对烟碱受体亚型的研究具有相当大的临床意义。我们对117个至少有一名精神分裂症患者的加拿大家庭中控制神经元高亲和力烟碱受体表达的CHRNA4和CHRNB2基因的多态性进行了分型。使用基于家系的关联策略，我们对这两个基因座进行了等位基因、单倍型和相互作用分析。在所测试的家庭中，这两个胆碱能基因相互作用，共同影响精神分裂症（P = 0.010），而单独一个基因都不足以 confer 易感性。我们目前的研究提供了直接证据，表明CHRNA4基因与CHRNB2受体基因相结合可能与精神分裂症有关。 （注：“confer”此处根据语境可能是“赋予”等意思，但结合上下文不太确定准确意思，可根据实际情况调整）
