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Transforming Growth Factor-ß₁ Gene Polymorphisms Are Associated with Disease Progression in Idiopathic Pulmonary Fibrosis

Servei de Pneumologia, Institut Clínic de Pneumología i Cirurgía Toràcica, Servei de Trasplantament Renal and Servei d'Otorinolaringologia, Hospital Clinic, Unitat d'Epidemiologia i Bioestadística, Fundació Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona; Servicio de Neumología, Hospital Universitario de la Princesa, Madrid; Servei de Pneumologia, Hospital Vall d'Hebrón, Barcelona; Servei de Pneumologia, Hospital Germans Trias i Pujol, Badalona; Servicio de Neumologia, Hospital Universitario Virgen del Rocío, Seville; and Departament de Neumologia, Hospital de Sant Pau, Barcelona, Spain

Correspondence and requests for reprints should be addressed to Antoni Xaubet, M.D., Servei de Pneumologia, Hospital Clinic, Villarroel 170, Barcelona 08036, Spain. E-mail: axaubet{at}clinic.ub.es

Transforming growth factor-ß₁ (TGF-ß₁) is a cytokine that plays a key role in the development of idiopathic pulmonary fibrosis. There have been reports on the presence of two genetic polymorphisms in the DNA sequence encoding the leader sequence of the TGF-ß₁ protein, located in codons 10 and 25. The objective of this study was to investigate the association between TGF-ß₁ gene polymorphisms in codons 10 and 25 and the susceptibility to idiopathic pulmonary fibrosis and the progression of the disease. Compared with healthy control subjects (n = 140), patients with idiopathic pulmonary fibrosis (n = 128) showed no significant deviations in genotype or allele frequencies. One hundred and ten patients with idiopathic pulmonary fibrosis were followed up for 30.3 ± 25 months. The presence of a proline allele at codon 10 was independently associated with a significant increase in alveolar arterial oxygen tension difference during follow-up, after controlling for the effect of treatment (coefficient = 0.59; 95% confidence intervals, 0.23 to 0.96; p = 0.002). These findings suggest that (1) TGF-ß₁ gene polymorphisms in codons 10 and 25 do not predispose to the development of idiopathic pulmonary fibrosis; and (2) TGF-ß₁ gene polymorphisms may affect disease progression in patients with idiopathic pulmonary fibrosis.

Key Words: genetic predisposition • interstitial lung diseases • pulmonary fibrosis

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