INHERITABILITY OF CYP3A ACTIVITY

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 基因决定因素对特定表型的重要性通常是通过比较同卵双胞胎和异卵双胞胎之间的变异性来研究的。然而，这种方法显然需要接触到双胞胎人口，这是有问题的。最近提出了一种替代方法，即在随机的、不相关的受试者群体中使用个体间和个体内的变异性(1-3)。显然，这是一个更容易学习的群体。 构成细胞色素P3A活性的个体间差异是有充分记录的，有证据表明，当暴露于诱导剂时，个体上调酶的能力有所不同(4)。这种CYP3A活性增加的遗传决定程度尚不清楚。 特定目标 1.确定任何遗传成分对CyP3A的构成和诱导活性的大小。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The importance of a genetic determinant to a particular phenotype has classically been investigated by comparing variability between identical and fraternal twins. However, this approach obviously requires access to a twin population, which is problematic. An alternative approach has recently been suggested that uses inter- and intra-individual variability within a population of random, unrelated subjects (1-3). This is obviously a more accessible group for study. Interindividual variability in constitutive CYP3A activity is well-documented and there is evidence that individuals vary in their ability to up-regulate the enzyme when exposed to an inducing agent (4). The extent of genetic determination of such an increase in CYP3A activity is unknown. Specific Aim 1. To determine the magnitude of any genetic component to the constitutive and induced activity of CYP3A.