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Among patients with cystic fibrosis (CF) the degree of pancreatic involvement is related to the particular mutation of the cystic fibrosis transmembrane conductance regulator gene (CFTR) involved. The severity of lung, liver, or gut disease, however, is much less determined by CFTR genotype. It seems probable, therefore, that other, ‘modifier’ genes may be involved in determining prognosis. Patients with CF have low concentrations of nitric oxide (NO) in expired air and decreased expression of the nitric oxide synthase 1 gene (NOS1) in upper airway epithelial cells. The number of dinucleotide GT repeats in the 5′-untranslated region (5-UTR) of this gene affects gene expression. Now researchers in Paris have shown that progression of lung disease may be greater in patients whose genes have fewer GT repeats in this region.
They studied 59 adults with CF and 59 healthy controls. On the basis of the number of GT repeats in the 5-UTR region of NOS1 they identified 19 different alleles, the number of repeats ranging from 18 to 36. The proportion of subjects with more than 27 repeats in 0, 1, or 2 alleles was 24%, 54%, and 22% among controls and 27%, 41%, and 32% among CF patients (no significant difference between patients and controls). A greater number of alleles with more than 27 repeats was associated with an increase in concentration of NO in expired air. Among patients with CF the annual percentage decrease in FEV1 in patients with 0, 1, or 2 alleles with more than 27 repeats was 3.3%, 3.2%, and 0.8%. The findings were independent of age, chronic airway colonisation with P aeruginosa or B cepacia, or CFTR genotype.
NOS1 genotype may modify the extent of lung damage in patients with cystic fibrosis.