INHERITABILITY OF CYP3A ACTIVITY

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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.