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Published ahead of print on May 13, 2003, doi:10.1164/rccm.200210-1165OC

Am. J. Respir. Crit. Care Med., Volume 168, Number 4, August 2003, 431-435

A more recent version of this article appeared on August 15, 2003
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Submitted on October 16, 2002
Accepted on May 3, 2003

TGF-beta 1 gene polymorphisms are associated to disease progression in idiopathic pulmonary fibrosis

Antoni Xaubet1*, Alejandra Marin-Arguedas1, Sergio Lario2, Julio Ancochea3, Ferran Morell4, Juan Ruiz-Manzano5, Eulogio Rodriguez-Becerra6, Jose M Rodriguez-Arias7, Pablo Inigo2, Sergi Sanz8, Josep M Campistol2, Joaquim Mullol9, and Cesar Picado1

1 Servei de Pneumologia, Hospital Clinic, Barcelona, Spain, 2 Servei de Trasplantament Renal, Hospital Clinic, Barcelona, Spain, 3 Servicio de Neumologia, Hospital Universitario de la Princesa, Madrid, Spain, 4 Servei de Pneumologia, Hospital Vall d'Hebron, Barcelona, Spain, 5 Servei de Pneumologia, Hospital Germans Trias i Pujol, Barcelona, Spain, 6 Servicio de Neumologia, Hospital Universitario Virgen del Rocio, Sevilla, Spain, 7 Departament de Neumologia, Hospital de Sant Pau, Barcelona, Spain, 8 Unitat d'Epidemiologia i Bioestadistica, Fundacio Clinic, IDIBAPS, Barcelona, Spain, 9 Servei d'Otorinolaringologia, Hospital Clinic, Barcelona, Spain

* To whom correspondence should be addressed. E-mail: axaubet{at}clinic.ub.es.

Transforming growth factor-beta 1 (TGF-{beta}1) is a cytokine which 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-{beta}1 protein, located in codons 10 and 25. The objective of this study was to investigate the association between TGF-{beta}1 gene polymorphisms in codons 10 and 25 and the susceptibility to idiopathic pulmonary fibrosis and the progression of the disease. Compared to healthy controls (n=140),idiopathic pulmonary fibrosis patients (n=128) showed no significant deviations in genotype o allele frequencies. One hundred and ten idiopathic pulmonary fibrosis patients were followed-up for 30.3 ± 25 months. The presence of Pro allele in codon 10 was independently associated with a significant increase in alveolar arterial oxygen tension difference during the follow-up, after controlling for the effect of the treatment (coefficient = 0.59, 95% confidence intervals 0.23 to 0.96, p = 0.002). These findings suggest that 1) TGF-{beta}1 gene polymorphisms in codons 10 and 25 do not predispose to the development of idiopathic pulmonary fibrosis; and 2) TGF-{beta}1 gene polymorphisms may affect disease progression in patients with idiopathic pulmonary fibrosis.
Key words: Interstitial lung diseases, genetic predisposition, pulmonary fibrosis




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