Polymorphisms in NOS-1 and NOS-3 genes may influence the cystic fibrosis severity?

Introduction: Cystic fibrosis(CF) has clinical variability associated with CFTR mutations, environmental factors and modifier genes, including genes associated with the nitric oxide pathway. Objective: To compare the CF severity with tandem repeat polymorphisms of the NOS-1 gene(AAT, TG1 and TG2) and -894G>T polymorphism in NOS-3 plus CFTR mutations by a bioinformatic tool. Method: 180 CF patients were included. The NOS-1 polymorphisms were analyzed in MegaBace1000 ® and NOS-3 by RFLP. Clinical markers: sex, scoresShwachman-Kulczycki, Kanga and Bhalla(EB), BMI, age, age at diagnosis, initial symptoms, first colonization by Pseudomonas aeruginosa (PA), colonization by microorganismsPA mucoid and non- mucoid, Achromobacter xylosoxidans (AX), Staphylococcus aureus , Burkolderia cepacia (BC), SpO2, spirometry and comorbiditiesnasal polyposis, pancreatic insufficiency, meconium ileus(MI), osteoporosis(O) and diabetes mellitus(DB). Statistical analysis: Fisher's exact, Mann-Whitney, Multifactor Dimensionalitty Reduction Test v2.0. Results: AAT= minor number of repetitions for allele 1(≤ 10) was associated with lower FEF25-75% and frequency of AX. Minor repetitions(≤1 ) in allele 2 was associated with higher frequency of MI. TG1= minor repetitions for allele 1(≤ 17) was associated with lower FEV1%, late onset of pulmonary disease, higher incidence of O. TG2= minor repetitions in allele 2(≤30) was associated with lower frequency of DB and BC, and higher FEV1/FVC. The T allele for the -894G>T was associated with early lung disease. There was gene interaction between TG1 and TG2 polymorphism plus CFTR mutations, and EB. Conclusion: Polymorphisms in NOS-1 and NOS-3 gene influence the CF severity.