Plasminogen alleles influence susceptibility to invasive aspergillosis

Author:

Zaas AK, Liao G, Chien JW, Weinberg C, Shore D, Giles SS, Marr KA, Usuka J, Burch LH, Perera L, Perfect JR, Peltz G, Schwartz DA

Date: 11 July 2008

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.

Link to DOI

Download the full article (Disclaimer)

This manuscript library of ~16,000 articles (1729-2024) related to Aspergillus and aspergillosis is intended for individual study only, and is provided as contribution to global understanding of the topic. Please refer to the publisher’s guidance about any other usage.