Human Genetic Susceptibility to Native Valve Staphylococcus aureus Endocarditis in Patients With S. aureus Bacteremia: Genome-Wide Association Study
Staphylococcus aureus infective endocarditis (SaIE) is a severe complication of S. aureus bacteremia (SAB) occurring in up to 22% of patients. Bacterial genetic factors and host conditions for SaIE have been intensely studied before; however, to date no study has focused on predisposing host genetic...
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| Language: | English |
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Frontiers Media S.A.
2018-04-01
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| Series: | Frontiers in Microbiology |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fmicb.2018.00640/full |
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| author | Karen Moreau Alisson Clemenceau Vincent Le Moing David Messika-Zeitoun David Messika-Zeitoun Paal S. Andersen Niels E. Bruun Niels E. Bruun Robert L. Skov Florence Couzon Coralie Bouchiat Coralie Bouchiat Marie L. Erpelding Alex van Belkum Yohan Bossé Yohan Bossé Xavier Duval Xavier Duval Francois Vandenesch Francois Vandenesch The French VIRSTA-AEPEI COFRASA Study Groups The Danish DANSAB Study Group |
| author_facet | Karen Moreau Alisson Clemenceau Vincent Le Moing David Messika-Zeitoun David Messika-Zeitoun Paal S. Andersen Niels E. Bruun Niels E. Bruun Robert L. Skov Florence Couzon Coralie Bouchiat Coralie Bouchiat Marie L. Erpelding Alex van Belkum Yohan Bossé Yohan Bossé Xavier Duval Xavier Duval Francois Vandenesch Francois Vandenesch The French VIRSTA-AEPEI COFRASA Study Groups The Danish DANSAB Study Group |
| author_sort | Karen Moreau |
| collection | DOAJ |
| description | Staphylococcus aureus infective endocarditis (SaIE) is a severe complication of S. aureus bacteremia (SAB) occurring in up to 22% of patients. Bacterial genetic factors and host conditions for SaIE have been intensely studied before; however, to date no study has focused on predisposing host genetic factors to SaIE. The present study aimed to identify genetic polymorphisms associated with SaIE by a Genome-Wide Association Study (GWAS) of 67 patients with definite native valve SaIE (cases) and 72 matched native valve patients with SAB but without IE (controls). All patients were enrolled in the VIRSTA cohort (Le Moing et al., 2015) study. Four single nucleotide polymorphisms (SNPs) located on chromosome 3 were associated with SaIE (P < 1 × 10-5) without reaching conventional genome-wide significance. For all, the frequency of the minor allele was lower in cases than in controls, suggesting a protective effect of the minor allele against SaIE. The same association was observed using an independent Danish verification cohort of SAB with (n = 57) and without (n = 123) IE. Ex vivo analysis of aortic valve tissues revealed that SaIE associated SNPs mentioned above were associated with significantly higher mRNA expression levels of SLC7A14, a predicted cationic amino acid transporter protein. Taken together, our results suggest an IE-protective effect of SNPs on chromosome 3 during the course of SAB. The effects of protective minor alleles may be mediated by increasing expression levels of SLC7A14 in valve tissues. We conclude that occurrence of SaIE may be the combination of a well-adapted bacterial genotype to a susceptible host. |
| first_indexed | 2024-12-19T18:21:19Z |
| format | Article |
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| issn | 1664-302X |
| language | English |
| last_indexed | 2024-12-19T18:21:19Z |
| publishDate | 2018-04-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Microbiology |
| spelling | doaj.art-8e487163d3cb42e5909cd0971d8223212022-12-21T20:10:59ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2018-04-01910.3389/fmicb.2018.00640345086Human Genetic Susceptibility to Native Valve Staphylococcus aureus Endocarditis in Patients With S. aureus Bacteremia: Genome-Wide Association StudyKaren Moreau0Alisson Clemenceau1Vincent Le Moing2David Messika-Zeitoun3David Messika-Zeitoun4Paal S. Andersen5Niels E. Bruun6Niels E. Bruun7Robert L. Skov8Florence Couzon9Coralie Bouchiat10Coralie Bouchiat11Marie L. Erpelding12Alex van Belkum13Yohan Bossé14Yohan Bossé15Xavier Duval16Xavier Duval17Francois Vandenesch18Francois Vandenesch19The French VIRSTA-AEPEICOFRASA Study GroupsThe Danish DANSAB Study GroupInternational Center for Infectiology Research, CNRS UMR5308, INSERM U1111, Ecole Normale Supérieure de Lyon, Université Lyon 1, Lyon, FranceInstitut Universitaire de Cardiologie et de Pneumologie de Québec – Université Laval, Quebec City, QC, CanadaDepartment for Infectious Diseases and Tropical Medicine, Centre Hospitalier, Universitaire de Montpellier, Montpellier, FranceDepartment of Cardiology, AP-HP, Bichat Hospital, Paris, FranceINSERM U698 and University Paris 7, Paris, FranceStatens Serum Institut, Copenhagen, DenmarkStatens Serum Institut, Copenhagen, DenmarkClinical Institute, Aalborg University, Aalborg, DenmarkStatens Serum Institut, Copenhagen, DenmarkInternational Center for Infectiology Research, CNRS UMR5308, INSERM U1111, Ecole Normale Supérieure de Lyon, Université Lyon 1, Lyon, FranceInternational Center for Infectiology Research, CNRS UMR5308, INSERM U1111, Ecole Normale Supérieure de Lyon, Université Lyon 1, Lyon, FranceCentre National de Référence des Staphylocoques, Centre de Biologie Est, Hospices Civils de Lyon, Lyon, FranceINSERM, CIC-1433 Clinical Epidemiology, CHRU Nancy, University of Lorraine, Nancy, France0Data Analytics Unit, bioMerieux, La Balme-les-Grottes, FranceInstitut Universitaire de Cardiologie et de Pneumologie de Québec – Université Laval, Quebec City, QC, Canada1Département de Médecine Moléculaire, Université Laval, Quebec City, QC, Canada2INSERM, UMR1138 IAME, CIC 1425, Université Paris Diderot, Paris, France3AP-HP, Hôpital Bichat-Claude Bernard, Paris, FranceInternational Center for Infectiology Research, CNRS UMR5308, INSERM U1111, Ecole Normale Supérieure de Lyon, Université Lyon 1, Lyon, FranceCentre National de Référence des Staphylocoques, Centre de Biologie Est, Hospices Civils de Lyon, Lyon, FranceStaphylococcus aureus infective endocarditis (SaIE) is a severe complication of S. aureus bacteremia (SAB) occurring in up to 22% of patients. Bacterial genetic factors and host conditions for SaIE have been intensely studied before; however, to date no study has focused on predisposing host genetic factors to SaIE. The present study aimed to identify genetic polymorphisms associated with SaIE by a Genome-Wide Association Study (GWAS) of 67 patients with definite native valve SaIE (cases) and 72 matched native valve patients with SAB but without IE (controls). All patients were enrolled in the VIRSTA cohort (Le Moing et al., 2015) study. Four single nucleotide polymorphisms (SNPs) located on chromosome 3 were associated with SaIE (P < 1 × 10-5) without reaching conventional genome-wide significance. For all, the frequency of the minor allele was lower in cases than in controls, suggesting a protective effect of the minor allele against SaIE. The same association was observed using an independent Danish verification cohort of SAB with (n = 57) and without (n = 123) IE. Ex vivo analysis of aortic valve tissues revealed that SaIE associated SNPs mentioned above were associated with significantly higher mRNA expression levels of SLC7A14, a predicted cationic amino acid transporter protein. Taken together, our results suggest an IE-protective effect of SNPs on chromosome 3 during the course of SAB. The effects of protective minor alleles may be mediated by increasing expression levels of SLC7A14 in valve tissues. We conclude that occurrence of SaIE may be the combination of a well-adapted bacterial genotype to a susceptible host.http://journal.frontiersin.org/article/10.3389/fmicb.2018.00640/fullinfectious endocarditisStaphylococcus aureusGWASbacteremiaSLC7A14 |
| spellingShingle | Karen Moreau Alisson Clemenceau Vincent Le Moing David Messika-Zeitoun David Messika-Zeitoun Paal S. Andersen Niels E. Bruun Niels E. Bruun Robert L. Skov Florence Couzon Coralie Bouchiat Coralie Bouchiat Marie L. Erpelding Alex van Belkum Yohan Bossé Yohan Bossé Xavier Duval Xavier Duval Francois Vandenesch Francois Vandenesch The French VIRSTA-AEPEI COFRASA Study Groups The Danish DANSAB Study Group Human Genetic Susceptibility to Native Valve Staphylococcus aureus Endocarditis in Patients With S. aureus Bacteremia: Genome-Wide Association Study Frontiers in Microbiology infectious endocarditis Staphylococcus aureus GWAS bacteremia SLC7A14 |
| title | Human Genetic Susceptibility to Native Valve Staphylococcus aureus Endocarditis in Patients With S. aureus Bacteremia: Genome-Wide Association Study |
| title_full | Human Genetic Susceptibility to Native Valve Staphylococcus aureus Endocarditis in Patients With S. aureus Bacteremia: Genome-Wide Association Study |
| title_fullStr | Human Genetic Susceptibility to Native Valve Staphylococcus aureus Endocarditis in Patients With S. aureus Bacteremia: Genome-Wide Association Study |
| title_full_unstemmed | Human Genetic Susceptibility to Native Valve Staphylococcus aureus Endocarditis in Patients With S. aureus Bacteremia: Genome-Wide Association Study |
| title_short | Human Genetic Susceptibility to Native Valve Staphylococcus aureus Endocarditis in Patients With S. aureus Bacteremia: Genome-Wide Association Study |
| title_sort | human genetic susceptibility to native valve staphylococcus aureus endocarditis in patients with s aureus bacteremia genome wide association study |
| topic | infectious endocarditis Staphylococcus aureus GWAS bacteremia SLC7A14 |
| url | http://journal.frontiersin.org/article/10.3389/fmicb.2018.00640/full |
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