Siervogel R M, Weinshilboum R, Wilson A F, Elston R C
Am J Med Genet. 1984 Oct;19(2):315-23. doi: 10.1002/ajmg.1320190214.
Five large families including 1,189 individuals were each ascertained through one proband with essential hypertension. Four of the probands were white and one was black. Erythrocyte catechol-o-methyltransferase (COMT) activity was measured in 551 family members. Standard statistical methods were used to investigate sex, age, and family differences in COMT activity. Maximum-likelihood methods were used to fit mixtures of normal distributions to COMT activity. COMT activity is distinctly bimodal. Pedigree segregation analyses were performed on the untransformed COMT values, their square roots, and natural logarithms in each family. In no family and under none of the three transformations was it possible to reject the hypothesis of Mendelian transmission of a major gene with two alleles in Hardy-Weinberg equilibrium. In most cases a genetic hypothesis with complete dominance or recessiveness, or a hypothesis of equal transmission probabilities was rejected. While the different transformations had a large effect on the skewness and kurtosis of the overall distribution of the data, they had little effect on the outcome of these segregation analyses. Therefore, this study strongly supports the concept that variation in COMT activity is due in large part to the effects of a major gene.
通过一名原发性高血压先证者确定了五个大家庭，共1189人。其中四名先证者为白人，一名为黑人。对551名家庭成员进行了红细胞儿茶酚 - O - 甲基转移酶（COMT）活性测定。采用标准统计方法研究COMT活性在性别、年龄和家庭方面的差异。运用最大似然法将正态分布混合模型拟合到COMT活性数据上。COMT活性呈现明显的双峰分布。对每个家庭中未转换的COMT值、其平方根和自然对数进行系谱分离分析。在任何一个家庭中，以及在三种转换方式中的任何一种情况下，都无法拒绝在哈迪 - 温伯格平衡中具有两个等位基因的主基因孟德尔遗传假说。在大多数情况下，完全显性或隐性的遗传假说，或等传递概率假说均被拒绝。虽然不同的转换方式对数据总体分布的偏度和峰度有很大影响，但对这些分离分析的结果影响很小。因此，本研究有力地支持了这样一种观点，即COMT活性的变异在很大程度上归因于一个主基因的作用。
