DELTA-F508 GENOTYPE DOES NOT PREDICT DISEASE SEVERITY IN AN ETHNICALLY DIVERSE CYSTIC-FIBROSIS POPULATION

Objective. As part of a study to determine population-based frequencie s of CFTR mutations in an ethnically diverse, midwestern cystic fibros is (CF) population, clinical histories were studied in 119 CF patients . Methodology. We sought to examine the association between genotype a s characterized by the Delta F508 and 11 other commonly occurring muta tions and clinical parameters including age at diagnosis, clinical pre sentation, sweat chloride level, chest roentgenogram score, clinical s cores, pulmonary function test results, percent weight for height, and presence of associated CF complications. Results. Age at diagnosis of CF was significantly associated with homozygosity for Delta F508 (mea n age at diagnosis +/- SE: 1.7 +/- 0.3 years for Delta F508/Delta F508 vs 3.9 +/- 0.9 years for Delta F508/other and other/other; P =.03). N o other age-adjusted clinical parameter was significantly associated w ith Delta F508 or any other genotype. Conclusion, These data suggest t hat in this sample of CF patients, Delta F508 genotype is not predicti ve of disease severity. The lack of association between disease severi ty and genotype in this ethnically diverse sample may reflect the pres ence of more severe undetected mutations in our sample, or the effects of modifying genes at other, non-CF loci.