Editorial

Boyle,; Lottenberg, Richard

doi:10.1006/meth.2000.0980

Cited by 7 publications

(1 citation statement)

References 24 publications

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“…Genetic differences that alter the coagulative function of plasminogen may also influence disease pathogenesis by promoting pulmonary hemorrhage and infarction. Immobilization of plasminogen on the pathogen surface allows for easier activation of this zymogen[10]. This brings the activated enzyme into close contact with key substrates in the basement membrane, which increases the virulence of bacteria [9],[16],[24] and other fungi [13],[14],[23].…”

Section: Discussionmentioning

confidence: 99%

Plasminogen Alleles Influence Susceptibility to Invasive Aspergillosis

et al. 2008

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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.

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