Thorax 2000;55:459-462 ( June )

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

Peter D Arkwright^a, Steven Laurie^b, Maurice Super^c, Vera Pravica^b, Martin J Schwarz^c, A Kevin Webb^d, Ian V Hutchinson^b

^a Academic Unit of Child Health, University of Manchester, St Mary's Hospital, Manchester M13 0JH, UK, ^b School of Biological Sciences, University of Manchester, Manchester M13 9PT, UK, ^c Department of Clinical Genetics, Royal Manchester Children's Hospital, Manchester M27 4HA, UK, ^d Bradbury Cystic Fibrosis Unit, Wythenshawe Hospital, Manchester M23 9LT, UK

Correspondence to: Dr P D Arkwright email:mdmfspda{at}fs1.scg.man.ac.uk

Received 8 September 1999; Returned to authors 11 November 1999; Revised version received 21 December 1999; Accepted for publication 20 January 2000

BACKGROUNDPolymorphisms in transforming growth factor (TGF)-₁ associated 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 undertaken to examine the association between TGF-₁ gene polymorphisms and the development of pulmonary dysfunction in patients with cystic fibrosis.
METHODSPolymorphisms in the TGF-₁ gene defining amino acids of codons 10 and 25 were determined by ARMS-PCR using DNA stored on 171 Caucasian patients who were homozygous for the F508 mutation of the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Clinical information on the patients was obtained from medical records.
RESULTSPatients with cystic fibrosis of a TGF-₁ high producer genotype for codon 10 had more rapid deterioration in lung function than those with a TGF-₁ low producer genotype. The relative risk of accelerated decline in forced expiratory volume in one second (FEV₁) to 50% predicted and forced vital capacity (FVC) to 70% predicted of patients with a high producer 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.
DISCUSSIONTGF-₁ genotypes may have a role in mediating pulmonary dysfunction in patients with cystic fibrosis. Further work is required to determine whether inhibition of TGF-₁ activity in these patients may slow disease progression.


Keywords: cystic fibrosis; transforming growth factor (TGF)-₁; polymorphisms; lung function tests

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© 2000 by Thorax
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