INHERITABILITY OF CYP3A ACTIVITY

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。通过比较同卵双胞胎和异卵双胞胎之间的差异，研究了遗传决定因素对特定表型的重要性。然而，这种方法显然需要访问双胞胎种群，这是有问题的。最近有人提出了另一种方法，即在随机、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）。这显然是一个更容易学习的群体。组成CYP3A活性的个体间变异性已被充分证明，有证据表明，当暴露于诱导剂时，个体上调该酶的能力有所不同(4)。基因决定CYP3A活性增加的程度尚不清楚。具体目标确定任何遗传成分对CYP3A组成和诱导活性的影响程度。

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.