Plasminogen alleles influence susceptibility to invasive aspergillosis

Aimee K. Zaas, Guochun Liao, Jason W. Chien, Clarice Weinberg, David Shore, Steven S. Giles, Kieren A. Marr, Jonathan Usuka, Lauranell H. Burch, Lalith Perera, John R. Perfect, Gary Peltz, David A. Schwartz

Research output: Contribution to journalArticle

Abstract

Invasive aspergillosis (IA) is a common and life-threatening infection in immunocompromised individuals. A number of environmental and epidemiologic risk factors for developing IA have been identified. However, genetic factors that affect risk for developing IA have not been clearly identified. We report that host genetic differences influence outcome following establishment of pulmonary aspergillosis in an exogenously immune suppressed mouse model. Computational haplotype-based genetic analysis indicated that genetic variation within the biologically plausible positional candidate gene plasminogen (Plg; Gene ID 18855) correlated with murine outcome. There was a single nonsynonymous coding change (Gly110Ser) where the minor allele was found in all of the susceptible strains, but not in the resistant strains. A nonsynonymous single nucleotide polymorphism (Asp472Asn) was also identified in the human homolog (PLG; Gene ID 5340). An association study within a cohort of 236 allogeneic hematopoietic stem cell transplant (HSCT) recipients revealed that alleles at this SNP significantly affected the risk of developing IA after HSCT. Furthermore, we demonstrated that plasminogen directly binds to Aspergillus fumigatus. We propose that genetic variation within the plasminogen pathway influences the pathogenesis of this invasive fungal infection.

Original languageEnglish (US)
Article numbere1000101
JournalPLoS genetics
Volume4
Issue number6
DOIs
StatePublished - Jun 2008
Externally publishedYes

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Molecular Biology
  • Genetics
  • Genetics(clinical)
  • Cancer Research

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  • Cite this

    Zaas, A. K., Liao, G., Chien, J. W., Weinberg, C., Shore, D., Giles, S. S., Marr, K. A., Usuka, J., Burch, L. H., Perera, L., Perfect, J. R., Peltz, G., & Schwartz, D. A. (2008). Plasminogen alleles influence susceptibility to invasive aspergillosis. PLoS genetics, 4(6), [e1000101]. https://doi.org/10.1371/journal.pgen.1000101