Genetic mutations in surfactant protein C are a rare cause of sporadic cases of IPF

• Published in: Thorax Vol. 59; no. 11; pp. 977 - 980
• Main Authors: Lawson, W E, Grant, S W, Ambrosini, V, Womble, K E, Dawson, E P, Lane, K B, Markin, C, Renzoni, E, Lympany, P, Thomas, A Q, Roldan, J, Scott, T A, Blackwell, T S, Phillips, J A, Loyd, J E, du Bois, R M
• Format: Journal Article
• Language: English
• Published: London BMJ 01-11-2004; BMJ Publishing Group LTD; BMJ Group
• Subjects: Age; Biological and medical sciences; Female; Gene Amplification; Heterozygote; Humans; Interstitial Lung Disease; Lavage; Lung diseases; Lung Diseases, Interstitial - genetics; Male; Medical sciences; Middle Aged; Mutation; Mutation - genetics; Patients; Pneumology; Polymorphism, Genetic; Proteins; Pulmonary fibrosis; Pulmonary Surfactant-Associated Protein C - genetics; Surfactants; United States > US; Case study; Sporadic; Pulmonary surfactant; Respiratory disease; Cardiovascular disease; Genetics; Protein C; Mutation; Protein A
• ISSN: 0040-6376; 1468-3296
• DOI: 10.1136/thx.2004.026336

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.