Zerba K E, Ferrell R E, Sing C F
Department of Human Genetics, University of Michigan, Ann Arbor 48109, USA.
Genetics. 1996 May;143(1):463-78. doi: 10.1093/genetics/143.1.463.
We analyzed the age-dependence of the estimates of the parameters of the genetic architecture of plasma ApoE levels associated with ApoE gene variation. Our study sample included 1988 individuals in multigeneration pedigrees from the Rochester, MN, population. We used a 30-yr sliding window across the age range (5-90 yr) to estimate the age dependency of parameters. Additive ApoE allelic variance of transformed plasma ApoE values for both genders, heritabilities for males and phenotypic and residual variance for females peaked in the 20-40-yr age windows and decreased significantly with age (P < 0.05). Phenotypic and residual variance for males and dominance variance for both genders did not vary significantly with age. All parameter estimates were significantly different from zero across all age windows for both genders. Most studies of ApoE have focused on its functions in the pathophysiology of coronary artery disease (CAD) in middle-aged and older individuals. Our findings suggest the greatest role of this gene is in determining phenotype differences among younger and middle-aged individuals. These observed genotypic effects on the plasma ApoE levels may contribute to age-dependent differences in physiological health, growth, and risk of disease.
我们分析了与载脂蛋白E（ApoE）基因变异相关的血浆ApoE水平遗传结构参数估计值的年龄依赖性。我们的研究样本包括来自明尼苏达州罗切斯特市人群的1988名多代家系个体。我们在年龄范围（5 - 90岁）内使用了一个30年的滑动窗口来估计参数的年龄依赖性。两性经转换的血浆ApoE值的加性ApoE等位基因方差、男性的遗传力以及女性的表型方差和残差方差在20 - 40岁年龄窗口达到峰值，并随年龄显著下降（P < 0.05）。男性的表型方差和残差方差以及两性的显性方差随年龄没有显著变化。所有年龄窗口中两性的所有参数估计值均显著不同于零。大多数关于ApoE的研究都集中在其在中老年个体冠状动脉疾病（CAD）病理生理学中的作用。我们的研究结果表明，该基因的最大作用在于决定年轻和中年个体之间的表型差异。这些观察到的基因型对血浆ApoE水平的影响可能导致生理健康、生长和疾病风险方面的年龄依赖性差异。
