Stengård J H, Zerba K E, Turner S T, Sing C F
National Public Health Institute, Department of Epidemiology and Health Promotion, Helsinki, Finland.
Ann Hum Genet. 1997 Mar;61(Pt 2):121-36. doi: 10.1046/j.1469-1809.1997.6120121.x.
We addressed the question: Is there evidence that allelic variation in a single unmeasured gene that has a large effect on maximal activity of erythrocyte sodium-lithium countertransport (Na-Li CNT) also has pleiotropic effects on variation in plasma triglyceride levels? Complex segregation analysis models that included plasma triglyceride levels as a covariate were considered as explanations for interindividual variation in Na-Li CNT. A sample of 711 healthy adults from 254 pedigrees enrolled in the Rochester Family Heart Study was selected for this study. The majority of the pedigrees supported the hypothesis that variations in a single unmeasured non-transmitted environmental factor have large effects on the Na-Li CNT distribution. Only gender-specific first-order covariate parameters were necessary in the complex segregation models suggesting that the form of the relationship between Na-Li CNT and plasma triglyceride level was not influenced by variation in the inferred environmental factor with large effects. Stratification of the sample by this inferred environmental factor resulted in three classes of individuals with significant differences in the distributions of coronary heart disease risk factor traits, as well as interindividual variation in both Na-Li CNT and plasma triglyceride levels. These results, along with other observations from the Rochester Family Heart Study sample, emphasize the complex and multifactorial nature of the causes of interindividual variation in Na-Li CNT. Our study further suggests that new research strategies are needed for studying the relationships between genetic and environmental variation and variation in quantitative traits such as Na-Li CNT that have been identified as risk factors for hypertension.
是否有证据表明，一个未测量的单个基因的等位基因变异对红细胞钠-锂逆向转运（Na-Li CNT）的最大活性有很大影响，同时对血浆甘油三酯水平的变异也具有多效性作用？将血浆甘油三酯水平作为协变量的复杂分离分析模型被视为对Na-Li CNT个体间变异的解释。本研究选取了罗切斯特家庭心脏研究中254个家系的711名健康成年人作为样本。大多数家系支持这样的假设，即一个未测量的非传递环境因素的变异对Na-Li CNT分布有很大影响。在复杂分离模型中仅需要性别特异性的一阶协变量参数，这表明Na-Li CNT与血浆甘油三酯水平之间关系的形式不受具有较大影响的推断环境因素变异的影响。根据这个推断环境因素对样本进行分层，结果产生了三类个体，他们在冠心病危险因素特征分布以及Na-Li CNT和血浆甘油三酯水平的个体间变异方面存在显著差异。这些结果，连同来自罗切斯特家庭心脏研究样本的其他观察结果，强调了Na-Li CNT个体间变异原因的复杂性和多因素性质。我们的研究进一步表明，需要新的研究策略来研究遗传和环境变异与已被确定为高血压危险因素的定量性状（如Na-Li CNT）变异之间的关系。
