Surfactant protein A and B genetic variants predispose to idiopathic pulmonary fibrosis

Moises Selman, Hung Mo Lin, Martha Montaño, Audrey L. Jenkins, Andrea Estrada, Zhenwu Lin, Guirong Wang, Susan L. DiAngelo, Xiaoxuan Guo, Todd M. Umstead, C. Max Lang, Annie Pardo, David S. Phelps, Joanna Floros

Research output: Contribution to journalArticlepeer-review

146 Scopus citations


Derangement in pulmonary surfactant or its components and alveolar collapse are common findings in idiopathic pulmonary fibrosis (IFF). Surfactant proteins play important roles in innate host defense and normal function of the lung. We examined associations between IFF and genetic polymorphic variants of surfactant proteins, SP-A1, SP-A2, SP-B, SP-C, and SP-D. One SP-A1 (6A4) allele and single nucleotide polymorphisms (SNPs) that characterize the 6A4 allele, and one SP-B (B1580_C) were found with higher frequency (P≤0.01) in nonsmoker and smoker IFF (n=84) subgroups, respectively, compared with healthy controls (n=194). To explore whether a tryptophan (present in 6A4) or an arginine (present in other SP-A1 alleles and in all SP-A2 alleles) at amino acid 219 alters protein behavior, two truncated proteins that varied only at amino acid 219 were oxidized by exposure to ozone. Differences in the absorption spectra (310-350 nm) between the two truncated recombinant SP-A proteins were observed both before and after protein oxidation, suggesting allele-specific aggregation differences attributable to amino acid 219. The SP-B SNP B1580_C (odds ratio:7.63; confidence interval: 1.64-35.4; P≤0.01), to be a risk factor for IFF smokers, has also been shown to be a risk factor for other pulmonary diseases. The SP-C and SP-D SNPs and SP-B-linked microsatellite markers studied did not associate with IFF. These findings indicate that surfactant protein variants may serve as markers to identify subgroups of patients at risk, and we speculate that these contribute to IFF pathogenesis.

Original languageEnglish (US)
Pages (from-to)542-550
Number of pages9
JournalHuman genetics
Issue number6
StatePublished - Nov 2003

All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)


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