Devor E J, Cloninger C R, Hoffman P L, Tabakoff B
Department of Psychiatry, Washington University School of Medicine, St. Louis, MO 63110.
Am J Hum Genet. 1991 Aug;49(2):372-7.
The activity of membrane-bound platelet adenylate cyclase, when stimulated in vitro by several compounds (including fluoride), is significantly reduced in alcoholics compared with control subjects. We have begun a study of the genetics of this enzyme activity. Complex segregation analysis of basal (unstimulated) platelet adenylate cyclase activity in families reveals a mode of inheritance that cannot be accounted for by a simple mixed model of transmission. By contrast, adenylate cyclase activity stimulated by fluoride ion reveals a single major locus effect with a modest multifactorial background. These results suggest that a single factor in the second-messenger pathway may (a) account for the majority of individual differences in stimulation of adenylate cyclase of fluoride and (b) help explain the reduced activities previously observed in alcoholics.
与对照组相比，酒精中毒者体外受几种化合物（包括氟化物）刺激时，膜结合血小板腺苷酸环化酶的活性显著降低。我们已开始对这种酶活性的遗传学进行研究。对家族中基础（未受刺激）血小板腺苷酸环化酶活性进行的复杂分离分析显示，其遗传模式无法用简单的混合传递模型来解释。相比之下，氟离子刺激的腺苷酸环化酶活性显示出单一主要基因座效应以及适度的多因素背景。这些结果表明，第二信使途径中的单一因素可能（a）解释了氟化物刺激腺苷酸环化酶时个体差异的大部分原因，（b）有助于解释先前在酒精中毒者中观察到的活性降低现象。
