TGF-β1 T869C Polymorphism May Affect Susceptibility to Idiopathic Pulmonary Fibrosis and Disease Severity
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Transforming growth factor-β1 (TGF-β1) is a key cytokine that plays a critical role in idiopathic pulmonary fibrosis (IPF). The genotypes of T869C polymorphism may be associated with the susceptibility to fibrotic lung disease.
We investigated a single-nucleotide polymorphism at exon 1 nucleotide position 29 (T → C) of the TGF-β1 gene. Eighty-five healthy controls and 85 subjects with surgically confirmed IPF were investigated using polymerase chain reaction and restriction enzyme fragment length polymorphism techniques.
The IPF patients consisted of 55 men and 30 women. The mean age was 61 ± 8 years. Fifty-one (60 %) of the 85 IPF patients were smokers and 34 were nonsmokers. The distribution of genotypes between IPF patients and controls was significantly different (IPF: TT 43.5 % and TC or CC 56.5 %; controls: TT 27.1 % and TC or CC 72.9 %, p = 0.037). TT genotype was significantly associated with decreased PaO2 and increased D(A–a)O2 upon initial diagnosis (p = 0.006 and 0.009, respectively). There was a positive association between TT genotype and IPF development (odds ratio [OR] = 2.1, 95 % confidence interval [CI] = 1.1–4.0, p = 0.028).
This study suggests that the TGF-β1 gene T869C polymorphism may affect susceptibility to IPF in Koreans. Larger studies are required to confirm the genetic association of TGF-β1 gene polymorphism and IPF.
KeywordsPulmonary fibrosis Idiopathic Transforming growth factor-β1 Polymorphism
This study was supported by a faculty research Grant (6-2005-0010) from the Department of Internal Medicine, Yonsei University, College of Medicine.
Conflict of interest
The authors have no conflicts of interest to declare.
- 4.Awad MR, El-Gamel A, Hasleton P, Turner DM, Sinnott PJ, Hutchinson IV (1998) 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 66(8):1014–1020PubMedCrossRefGoogle Scholar
- 5.Cambien F, Ricard S, Troesch A, Mallet C, Generenaz L, Evans A, Arveiler D, Luc G, Ruidavets JB, Poirier O (1996) Polymorphisms of the transforming growth factor-beta 1 gene in relation to myocardial infarction and blood pressure. The Etude Cas-Temoin de l’Infarctus du Myocarde (ECTIM) Study. Hypertension 28(5):881–887PubMedCrossRefGoogle Scholar
- 9.Xaubet A, Marin-Arguedas A, Lario S, Ancochea J, Morell F, Ruiz-Manzano J, Rodriguez-Becerra E, Rodriguez-Arias JM, Inigo P, Sanz S, Campistol JM, Mullol J, Picado C (2003) Transforming growth factor-beta1 gene polymorphisms are associated with disease progression in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 168(4):431–435PubMedCrossRefGoogle Scholar
- 10.American Thoracic Society (ATS), European Respiratory Society (ERS) (2002) American Thoracic Society/European Respiratory Society International Multidisciplinary consensus classification of the idiopathic interstitial pneumonias. This joint statement of the American Thoracic Society (ATS), and the European Respiratory Society (ERS) was adopted by the ATS board of directors, June 2001 and by the ERS Executive Committee, June 2001. Am J Respir Crit Care Med 165(2):277–304Google Scholar
- 12.Raghu G, Collard HR, Egan JJ, Martinez FJ, Behr J, Brown KK, Colby TV, Cordier JF, Flaherty KR, Lasky JA, Lynch DA, Ryu JH, Swigris JJ, Wells AU, Ancochea J, Bouros D, Carvalho C, Costabel U, Ebina M, Hansell DM, Johkoh T, Kim DS, King TE Jr, Kondoh Y, Myers J, Muller NL, Nicholson AG, Richeldi L, Selman M, Dudden RF, Griss BS, Protzko SL, Schunemann HJ (2011) An official ATS/ERS/JRS/ALAT statement: idiopathic pulmonary fibrosis: evidence-based guidelines for diagnosis and management. Am J Respir Crit Care Med 183(6):788–824PubMedCrossRefGoogle Scholar
- 13.Franko AJ, Sharplin J, Ghahary A, Barcellos-Hoff MH (1997) 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 147(2):245–256PubMedCrossRefGoogle Scholar
- 15.Yamada Y, Miyauchi A, Goto J, Takagi Y, Okuizumi H, Kanematsu M, Hase M, Takai H, Harada A, Ikeda K (1998) Association of a polymorphism of the transforming growth factor-beta1 gene with genetic susceptibility to osteoporosis in postmenopausal Japanese women. J Bone Miner Res 13(10):1569–1576PubMedCrossRefGoogle Scholar