Progression and severity of lung disease differs markedly and early between patients with cystic fibrosis (CF). We investigated the hypothesis that polymorphisms in the detoxifying enzymes ...glutathione-S-transferase (GST) could influence phenotypic presentation of lung disease in CF.
Genotypes for GSTM1, GSTM3, GSTP1 and GSTT1 were determined in a cohort of 146 children with CF by PCR-based methods. Pulmonary function, assessed by spirometric measures of forced expiratory volume in one second (FEV1) and forced vital capacity (FVC), was analysed in children at the age of 9.
No association between spirometric measurements, and GSTM1, GSTP1 or GSTT1 genotypes was found. As compared with patients homozygous for GSTM3*A allele, CF children carrying the GSTM3*B allele displayed a significant better lung function, assessed by both mean values of FEV1 and of FVC (respectively P = 0.01 and P = 0.002). These correlations remained significant after adjustment for potential confounding factors (respectively adjusted P = 0.008 and P = 0.002) and also in subgroups of CF patients who carry the deltaF508 CFTR mutation. Haplotype analysis of GSTM3 in combination with GSTM1 indicated that the positive impact of GSTM3*B allele on pulmonary performances was barely influenced by the GSTM1 genotypes of CF children.
These data provide the first evidence suggesting that polymorphism of the GSTM3 gene contributes to clinical severity in CF, which may have prognostic significance and could prompt to start a more targeted therapy in young patients with CF.
The circumstances leading to the diagnosis of cystic fibrosis are sensibly going to be modified in France, with the generalisation of systematic neonatal screening. Indeed, close to 95% of patients ...will be diagnosed in the neonatal period. Those who are missed by this screening often have a form of disease that is said to be moderate, with specific mutations, and without pancreatic insufficiency. However be the mode of revelation, the diagnosis should be confirmed by a positive sweat test with an elevated level of chlorine, and (or) the presence of 2 mutations in the gene causing the illness. Early diagnosis by screening only makes sense if the patients are followed in specialised centres of care, accredited by the professional bodies. It is in all likelihood to be at this price that the results, in terms of median survival, will improve in our country.
