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INTERSTITIAL LUNG DISEASE |
1 Department of Medicine, Division of Allergy, Pulmonary and Critical Care Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA
2 Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, TN, USA
3 Department of Pediatrics, Division of Medical Genetics, Vanderbilt University School of Medicine, Nashville, TN, USA
4 Department of Biostatistics, Vanderbilt University School of Medicine, Nashville, TN, USA
5 Department of Veterans Affairs Medical Center, Nashville, TN, USA
6 BioVentures Inc, Murfreesboro, TN, USA
7 Department of Thoracic Diseases, Unit of Respiratory Medicine, S Orsola-Malgpghi Hospital, University of Bologna, Italy
8 Royal Brompton Hospital and Imperial College of Science, Technology and Medicine, London, UK
Correspondence to:
Correspondence to:
Dr J E Loyd
Professor of Medicine, Allergy, Pulmonary and Critical Care Medicine, Vanderbilt University School of Medicine, T-1217 MCN, Nashville, TN 37232-2650, USA; jim.loyd{at}vanderbilt.edu
Background: While idiopathic pulmonary fibrosis (IPF) is one of the most common forms of interstitial lung disease, the aetiology of IPF is poorly understood. Familial cases of pulmonary fibrosis suggest a genetic basis for some forms of the disease. Recent reports have linked genetic mutations in surfactant protein C (SFTPC) with familial forms of pulmonary fibrosis, including one large family in which a number of family members were diagnosed with usual interstitial pneumonitis (UIP), the pathological correlate to IPF. Because of this finding in familial cases of pulmonary fibrosis, we searched for SFTPC mutations in a cohort of sporadic cases of UIP and non-specific interstitial pneumonitis (NSIP).
Methods: The gene for SFTPC was sequenced in 89 patients diagnosed with UIP, 46 patients with NSIP, and 104 normal controls.
Results: Ten single nucleotide polymorphisms in the SFTPC sequence were found in IPF patients and not in controls. Only one of these created an exonic change resulting in a change in amino acid sequence. In this case, a T to C substitution resulted in a change in amino acid 73 of the precursor protein from isoleucine to threonine. Of the remaining polymorphisms, one was in the 5' UTR, two were exonic without predicted amino acid sequence changes, and six were intronic. One intronic mutation suggested a potential enhancement of a splicing site.
Conclusions: Mutations in SFTPC are identified infrequently in this patient population. These findings indicate that SFTPC mutations do not contribute to the pathogenesis of IPF in the majority of sporadic cases.
Abbreviations: ESE, exonic splicing enhancer; FPF, familial pulmonary fibrosis; IPF, idiopathic pulmonary fibrosis; NSIP, non-specific interstitial pneumonitis; SFTPC, surfactant protein C; SNP, single nucleotide polymorphism; UIP, usual interstitial pneumonitis
Keywords: interstitial pulmonary fibrosis; familial pulmonary fibrosis; genetics; surfactant protein C (SFTPC)
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