Cystic fibrosis (CF) is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Over 500 different mutations have been identified in the CFTR gene. However, the severity of pulmonary disease in CF patients is highly variable, even in individuals with the same genotype. This data suggests that there are additional genetic and/or environmental factors that contribute to the severity of CF lung disease. It has also been shown that the severity of lung disease is significantly concordant amongst CF siblings, suggesting that a major genetic factor is present. Furthermore, analysis of the effect of genetic background in CFTR-deficient mice indicates that other genes play an important role in the severity of disease.
The aim of this project is to identify the genetic basis of the heterogeneity in CF patients. We have obtained DNA from several cohorts of CF patients and classified these patients as having mild or severe lung disease based on their age and lung function. We have analyzed these patient groups for associations with genetic markers for genes involved in the immune response. Patients with mild disease have an increased frequency of the HLA DQA 101 allele and a decreased frequency of the 301 allele. This suggests that the HLA locus may contribute to the severity of lung disease in CF patients.
