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. 2000 Jun;55(6):459–462. doi: 10.1136/thorax.55.6.459

TGF-β1 genotype and accelerated decline in lung function of patients with cystic fibrosis

P Arkwright 1, S Laurie 1, M Super 1, V Pravica 1, M Schwarz 1, A Webb 1, I Hutchinson 1
PMCID: PMC1745768  PMID: 10817792

Abstract

BACKGROUND—Polymorphisms in transforming growth factor (TGF)-β1 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-β1 gene polymorphisms and the development of pulmonary dysfunction in patients with cystic fibrosis.
METHODS—Polymorphisms in the TGF-β1 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 ΔF508 mutation of the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Clinical information on the patients was obtained from medical records.
RESULTS—Patients with cystic fibrosis of a TGF-β1 high producer genotype for codon 10 had more rapid deterioration in lung function than those with a TGF-β1 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.
DISCUSSION—TGF-β1 genotypes may have a role in mediating pulmonary dysfunction in patients with cystic fibrosis. Further work is required to determine whether inhibition of TGF-β1 activity in these patients may slow disease progression.



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Selected References

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  1. Awad M. R., El-Gamel A., Hasleton P., Turner D. M., Sinnott P. J., Hutchinson I. V. Genotypic variation in the transforming growth factor-beta1 gene: association with transforming growth factor-beta1 production, fibrotic lung disease, and graft fibrosis after lung transplantation. Transplantation. 1998 Oct 27;66(8):1014–1020. doi: 10.1097/00007890-199810270-00009. [DOI] [PubMed] [Google Scholar]
  2. Bayer E. M., Herr W., Kanzler S., Waldmann C., Meyer Zum Büschenfelde K. H., Dienes H. P., Lohse A. W. Transforming growth factor-beta1 in autoimmune hepatitis: correlation of liver tissue expression and serum levels with disease activity. J Hepatol. 1998 May;28(5):803–811. doi: 10.1016/s0168-8278(98)80230-4. [DOI] [PubMed] [Google Scholar]
  3. Corrin B., Butcher D., McAnulty B. J., Dubois R. M., Black C. M., Laurent G. J., Harrison N. K. Immunohistochemical localization of transforming growth factor-beta 1 in the lungs of patients with systemic sclerosis, cryptogenic fibrosing alveolitis and other lung disorders. Histopathology. 1994 Feb;24(2):145–150. doi: 10.1111/j.1365-2559.1994.tb01293.x. [DOI] [PubMed] [Google Scholar]
  4. El-Gamel A., Awad M., Sim E., Hasleton P., Yonan N., Egan J., Deiraniya A., Hutchinson I. V. Transforming growth factor-beta1 and lung allograft fibrosis. Eur J Cardiothorac Surg. 1998 Apr;13(4):424–430. doi: 10.1016/s1010-7940(98)00048-7. [DOI] [PubMed] [Google Scholar]
  5. Franko A. J., Sharplin J., Ghahary A., Barcellos-Hoff M. H. Immunohistochemical localization of transforming growth factor beta and tumor necrosis factor alpha in the lungs of fibrosis-prone and "non-fibrosing" mice during the latent period and early phase after irradiation. Radiat Res. 1997 Feb;147(2):245–256. [PubMed] [Google Scholar]
  6. Grainger D. J., Heathcote K., Chiano M., Snieder H., Kemp P. R., Metcalfe J. C., Carter N. D., Spector T. D. Genetic control of the circulating concentration of transforming growth factor type beta1. Hum Mol Genet. 1999 Jan;8(1):93–97. doi: 10.1093/hmg/8.1.93. [DOI] [PubMed] [Google Scholar]
  7. Ignotz R. A., Massagué J. Transforming growth factor-beta stimulates the expression of fibronectin and collagen and their incorporation into the extracellular matrix. J Biol Chem. 1986 Mar 25;261(9):4337–4345. [PubMed] [Google Scholar]
  8. Kanzler S., Lohse A. W., Keil A., Henninger J., Dienes H. P., Schirmacher P., Rose-John S., zum Büschenfelde K. H., Blessing M. TGF-beta1 in liver fibrosis: an inducible transgenic mouse model to study liver fibrogenesis. Am J Physiol. 1999 Apr;276(4 Pt 1):G1059–G1068. doi: 10.1152/ajpgi.1999.276.4.G1059. [DOI] [PubMed] [Google Scholar]
  9. Kopp J. B., Factor V. M., Mozes M., Nagy P., Sanderson N., Böttinger E. P., Klotman P. E., Thorgeirsson S. S. Transgenic mice with increased plasma levels of TGF-beta 1 develop progressive renal disease. Lab Invest. 1996 Jun;74(6):991–1003. [PubMed] [Google Scholar]
  10. Perrey C., Pravica V., Sinnott P. J., Hutchinson I. V. Genotyping for polymorphisms in interferon-gamma, interleukin-10, transforming growth factor-beta 1 and tumour necrosis factor-alpha genes: a technical report. Transpl Immunol. 1998 Sep;6(3):193–197. doi: 10.1016/s0966-3274(98)80045-2. [DOI] [PubMed] [Google Scholar]
  11. Perrey C., Turner S. J., Pravica V., Howell W. M., Hutchinson I. V. ARMS-PCR methodologies to determine IL-10, TNF-alpha, TNF-beta and TGF-beta 1 gene polymorphisms. Transpl Immunol. 1999 Jun;7(2):127–128. doi: 10.1016/s0966-3274(99)80030-6. [DOI] [PubMed] [Google Scholar]
  12. Phan S. H., Kunkel S. L. Lung cytokine production in bleomycin-induced pulmonary fibrosis. Exp Lung Res. 1992 Jan-Mar;18(1):29–43. doi: 10.3109/01902149209020649. [DOI] [PubMed] [Google Scholar]
  13. Qi Z., Atsuchi N., Ooshima A., Takeshita A., Ueno H. Blockade of type beta transforming growth factor signaling prevents liver fibrosis and dysfunction in the rat. Proc Natl Acad Sci U S A. 1999 Mar 2;96(5):2345–2349. doi: 10.1073/pnas.96.5.2345. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Roberts A. B., Lamb L. C., Newton D. L., Sporn M. B., De Larco J. E., Todaro G. J. Transforming growth factors: isolation of polypeptides from virally and chemically transformed cells by acid/ethanol extraction. Proc Natl Acad Sci U S A. 1980 Jun;77(6):3494–3498. doi: 10.1073/pnas.77.6.3494. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Zielenski J., Tsui L. C. Cystic fibrosis: genotypic and phenotypic variations. Annu Rev Genet. 1995;29:777–807. doi: 10.1146/annurev.ge.29.120195.004021. [DOI] [PubMed] [Google Scholar]

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