Plasminogen alleles influence susceptibility to invasive aspergillosis.
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 r...
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2008-06-01
|
| Series: | PLoS Genetics |
| Online Access: | http://europepmc.org/articles/PMC2423485?pdf=render |
| _version_ | 1818391286756933632 |
|---|---|
| author | 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 |
| author_facet | 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 |
| author_sort | Aimee K Zaas |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-14T05:11:07Z |
| format | Article |
| id | doaj.art-353cec01b2e74dfd894193c0000423c2 |
| institution | Directory Open Access Journal |
| issn | 1553-7390 1553-7404 |
| language | English |
| last_indexed | 2024-12-14T05:11:07Z |
| publishDate | 2008-06-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Genetics |
| spelling | doaj.art-353cec01b2e74dfd894193c0000423c22022-12-21T23:15:58ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042008-06-0146e100010110.1371/journal.pgen.1000101Plasminogen alleles influence susceptibility to invasive aspergillosis.Aimee K ZaasGuochun LiaoJason W ChienClarice WeinbergDavid ShoreSteven S GilesKieren A MarrJonathan UsukaLauranell H BurchLalith PereraJohn R PerfectGary PeltzDavid A SchwartzInvasive 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.http://europepmc.org/articles/PMC2423485?pdf=render |
| spellingShingle | 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 Plasminogen alleles influence susceptibility to invasive aspergillosis. PLoS Genetics |
| title | Plasminogen alleles influence susceptibility to invasive aspergillosis. |
| title_full | Plasminogen alleles influence susceptibility to invasive aspergillosis. |
| title_fullStr | Plasminogen alleles influence susceptibility to invasive aspergillosis. |
| title_full_unstemmed | Plasminogen alleles influence susceptibility to invasive aspergillosis. |
| title_short | Plasminogen alleles influence susceptibility to invasive aspergillosis. |
| title_sort | plasminogen alleles influence susceptibility to invasive aspergillosis |
| url | http://europepmc.org/articles/PMC2423485?pdf=render |
| work_keys_str_mv | AT aimeekzaas plasminogenallelesinfluencesusceptibilitytoinvasiveaspergillosis AT guochunliao plasminogenallelesinfluencesusceptibilitytoinvasiveaspergillosis AT jasonwchien plasminogenallelesinfluencesusceptibilitytoinvasiveaspergillosis AT clariceweinberg plasminogenallelesinfluencesusceptibilitytoinvasiveaspergillosis AT davidshore plasminogenallelesinfluencesusceptibilitytoinvasiveaspergillosis AT stevensgiles plasminogenallelesinfluencesusceptibilitytoinvasiveaspergillosis AT kierenamarr plasminogenallelesinfluencesusceptibilitytoinvasiveaspergillosis AT jonathanusuka plasminogenallelesinfluencesusceptibilitytoinvasiveaspergillosis AT lauranellhburch plasminogenallelesinfluencesusceptibilitytoinvasiveaspergillosis AT lalithperera plasminogenallelesinfluencesusceptibilitytoinvasiveaspergillosis AT johnrperfect plasminogenallelesinfluencesusceptibilitytoinvasiveaspergillosis AT garypeltz plasminogenallelesinfluencesusceptibilitytoinvasiveaspergillosis AT davidaschwartz plasminogenallelesinfluencesusceptibilitytoinvasiveaspergillosis |