Patients with CF have mutations in both copies of their CF transmembrane regulator (CFTR) genes. CF patients also have measurable abnormalities in the amount of fatty acids (FAs) in their blood. Some FAs in the body can be converted to substances that participate in inflammation, and biologic markers of inflammation have also been found to be abnormal in CF patients. None of these abnormalities are found in healthy people without CF. Similar abnormalities in FA levels abd signs of inflammation have been described in CF animal models in organs commonly affected in CF, such as the lung and pancreas. Therefore it is possible that anbormal fatty acids could also play a role in CF disease manifestations in humans. In this study, the purpose of Aims 1&2 is to measure fatty acids in plasma, red blood cells and nasal epithelium (as a representative tissue of lung epithelium) and examine the relationship between these fatty acid levels and the severiyt of pulmonary disease in delta F508 homozygous CF patients. Only delta F508 homozygous patients will be included in Aims 1&2 in order to control for CFTR genotype in the search for genetic modifiers of CFTR that could play a role in the relationship between fatty acid imbalance and CF pulmonary disease.
In Aim 3, the same fatty acid levels in twins and other siblings with CF will be measured and compared to their pulmonary disease severity. Because of the inherent genetic similarity of twins and siblings, it is possible to determine the relative proportion of their disease manifestations that are due to environment and genetic factors by contrasting this relationship (fatty acid abnormalities and pulmonary disease) within and between twin and sibling pairs. These efforts will help us better understand CF pathogenesis and the influence that fatty acid abnormalities may have on the severity of pulmonary disease. It is anticipated that these results will head to further studies to 1) define the long-term relationship between fatty acid abnormalities and the natural course of deteriorating of CF pulmonary disease and 2) to potentially alter these fatty acid abnormaltiies in CF patients with the hope of improving disease outcome and ultimately survival.
