Grant: Travel Awards - Institute Community Support

Cystic fibrosis (CF) is an inherited disease causing a build-up of thick, sticky mucus in the lung, digestive tract, and other areas of the body. This increases susceptibility to bacterial infection in the lung, leading to early death due to chronic lung disease. CF patients who have the same alteration in the primary causal gene may have a very different clinical course. One CF patient may have very mild lung disease and infrequent lung infections, while another with the same alteration may have frequent lung infections accompanied by great decreases in lung function. In our previous studies we performed a comprehensive search through all of the human chromosomes for genes (known as modifier genes) that cause some CF patients to become sicker faster than others. Particular regions of specific chromosomes were identified as influencing lung function but these regions each contain a handful of genes and the specific genes responsible for modifying disease severity remain to be determined. One region of the human chromosome 20 which has been identified as being potentially relevant to CF contains the SPLUNC1 (BPIFA1) and LPLUNC1 (BPIFB1) genes. Both genes are thought to be involved in fighting bacterial infection in the lungs. Genetic variants in these genes have been associated with milder lung disease in CF patients. These variants may result in higher levels of SPLUNC1 and LPLUNC1 which could help rid the lungs of bacterial infection. To test this hypothesis, we measured SPLUNC1 and LPLUNC1 levels in CF and non-CF individuals with different genetic variants. We found that a genetic variant in the SPLUNC1 gene was associated with higher levels of the gene. We also found that both SPLUNC1 and LPLUNC1 have higher levels of expression in CF lung samples when compared to non-CF samples. If PLUNCs are shown to be protective against bacterial infection in the lung, aerosolized forms of these molecules could be extremely useful in CF therapy.