Human Genetic Susceptibility to Native Valve Staphylococcus aureus Endocarditis in Patients With S. aureus Bacteremia: Genome-Wide Association Study
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Human Genetic Susceptibility to Native Valve Staphylococcus aureus Endocarditis in Patients With S. aureus Bacteremia : Genome-Wide Association Study. / Moreau, Karen; Clemenceau, Alisson; Le Moing, Vincent; Messika-Zeitoun, David; Andersen, Paal S.; Bruun, Niels E.; Skov, Robert L.; Couzon, Florence; Bouchiat, Coralie; Erpelding, Marie L.; van Belkum, Alex; Bossé, Yohan; Duval, Xavier; Vandenesch, François; The French VIRSTA-AEPEI, COFRASA Study Groups and the Danish DANSAB Study Group ; Johansen, Helle Krogh; Hassager, Christian; Ullum, Henrik.
In: Frontiers in Microbiology, Vol. 9, 640, 04.04.2018, p. 1-11.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Human Genetic Susceptibility to Native Valve Staphylococcus aureus Endocarditis in Patients With S. aureus Bacteremia
T2 - Genome-Wide Association Study
AU - Moreau, Karen
AU - Clemenceau, Alisson
AU - Le Moing, Vincent
AU - Messika-Zeitoun, David
AU - Andersen, Paal S.
AU - Bruun, Niels E.
AU - Skov, Robert L.
AU - Couzon, Florence
AU - Bouchiat, Coralie
AU - Erpelding, Marie L.
AU - van Belkum, Alex
AU - Bossé, Yohan
AU - Duval, Xavier
AU - Vandenesch, François
AU - The French VIRSTA-AEPEI, COFRASA Study Groups and the Danish DANSAB Study Group
AU - Johansen, Helle Krogh
AU - Hassager, Christian
AU - Ullum, Henrik
PY - 2018/4/4
Y1 - 2018/4/4
N2 - 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.
AB - 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.
KW - Bacteremia
KW - GWAS
KW - Infectious endocarditis
KW - SLC7A14
KW - Staphylococcus aureus
UR - http://www.scopus.com/inward/record.url?scp=85045025375&partnerID=8YFLogxK
U2 - 10.3389/fmicb.2018.00640
DO - 10.3389/fmicb.2018.00640
M3 - Journal article
C2 - 29670602
AN - SCOPUS:85045025375
VL - 9
SP - 1
EP - 11
JO - Frontiers in Microbiology
JF - Frontiers in Microbiology
SN - 1664-302X
M1 - 640
ER -
ID: 203589757