Objectives: To compare Cystic Fibrosis (CF) severity with NOS-1 polymorphisms (pol.) (AAT, TG1 and TG2) and CFTR interaction. Methods: 181 patients included. The NOS-1 pol. was analyzed by Megabace1000® sequencer. Variables: sex, race, scores [Shwachman-Kulczycki, Kanga and Bhalla (EB)], BMI, age, diagnosis age, first symptoms (digestive and pulmonary), first P. aeruginosa, microorganisms (P. aeruginosa mucoid and non-mucoid, A. xylosoxidans, S. aureus, B. cepacia), SaO2, spirometry and comorbidities (nasal polyps, osteoporosis, meconium ileus, pancreatic insufficiency, diabetes mellitus). Statistical analysis: MDR2.0 and MDRPT0.4.7 software. Numerical data: classified by the median. Categorical data: presence or absence (bacteria and comorbidities). Multiple genes analysis in disease with clinical variation, like CF, allows greater understanding of phenotypic diversity. The analysis of all alleles for NOS-1 and CFTR did not show association. The same was observed to alleles with more repetitions in NOS-1. However, alleles with minor repetitions in NOS-1 and CFTR showed association with the race and age. For race, the ratio between Caucasian and non-Caucasian was not similar and the p-value becomes irrelevant. Regarding age, only the CFTR was associated. Finally, there was association of minor repetitions to the TG1 and TG2 pol. in NOS-1, along with CFTR, with BS (measures the degree of impairment of structure bronchopulmonary) (Ratio: 0.954; Ball Test. Acc: 0.643, p: 0.033). The BS is a marker of early lung disease and is associated with the clinical severity, being considered an important factor in clinical prediction. Conclusion: NOS-1 and CFTR interaction influence BS value in CF. WS20.6 High throughput screening as a source for novel cystic fibrosis therapeutic targets H.M. Botelho1,2, S. Dahimene1,2, I. Uliyakina1,2, B. Neumann2, C. Tischer2, R. Pepperkok2, M.D. Amaral1. 1University of Lisboa, Faculty of Sciences (FCUL), BioFIG-Center for Biodiversity, Functional and Integrative Genomics, Lisboa, Portugal; 2European Molecular Biology Laboratory (EMBL), Cell Biology Biophysics Unit and Advanced Light Microscopy Facility (ALMF), Heidelberg, Germany