TGF-beta(1) genotype and accelerated decline in lung function of patients with cystic fibrosis

Background-Polymorphisms in transforming growth factor (TGF)-beta(1) associ ated with variations in cytokine levels are Linked to fibrosis in a number of tissues. However, the contribution of this cytokine to organ fibrosis in patients with cystic fibrosis is presently unclear. This study was underta ken to examine the association between TGF-beta(1) gene polymorphisms and t he development of pulmonary dysfunction in patients with cystic fibrosis. Methods-Polymorphisms in the TGF-beta(1) gene defining amino acids of codon s 10 and 25 were determined by ARMS-PCR using DNA stored on 171 Caucasian p atients who were homozygous for the Delta F508 mutation of the cystic fibro sis transmembrane conductance regulator (CFTR) gene. Clinical information o n the patients was obtained from medical records. Results-Patients with cystic fibrosis of a TGF-beta(1) high producer genoty pe for codon 10 had more rapid deterioration in lung function than those wi th a TGF-beta(1) low producer genotype. The relative risk of accelerated de cline in forced expiratory volume in one second (FEV1) to 50% predicted and forced vital capacity (FVC) to 70% predicted of patients with a high produ cer genotype was 1.74 (95% CI 1.11 to 2.73) compared with 1.95 (95% CI 1.24 to 3.06) for those with a low producer genotype. Discussion-TGF-beta(1) genotppes may have a role in mediating pulmonary dys function in patients with cystic fibrosis. Further work is required to dete rmine whether inhibition of TGF-beta(1) activity in these patients may slow disease progression.