The overarching goals of this research proposal are to better understand the genetic predisposition to sarcoidosis and to further elucidate the contribution of abnormal apoptosis to human diseases. The guiding hypothesis is that dysregulation of apoptosis caused by specific genetic polymorphisms contributes to the development of sarcoidosis. The hypothesis further states that this contribution occurs via elimination of the T cells and macrophages required to confine antigen. There are three specific aims for this project. First, correlations will be established between levels of expression of two key apoptosis-related proteins (Fas and TNF-a), the presence and amount of apoptosis, and the presence of specific Fas and TNF-a promoter polymorphisms. These measurements will be made in peripheral T cells and monocytes. The second specific aim involves the use of a case-control study to determine the association of the Fas and TNF-a promoter polymorphisms and sarcoidosis. Finally, the third specific aim will use a case-comparison study to establish the association between the presence of the same polymorphisms and the severity of disease.
