Genetic variability in beta-defensins is not associated with susceptibility to Staphylococcus aureus bacteremia.
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INTRODUCTION: Human beta-defensins are key components of human innate immunity to a variety of pathogens, including Staphylococcus aureus. The aim of the present study was to investigate a potential association between gene variations in DEFB1 and DEFB103/DEFB4 and the development of S. aureus bacteremia (SAB) employing a case-control design. METHODS: Cases were unique patients with documented SAB, identified with the National S. aureus Bacteremia Register, a comprehensive dataset of all episodes of community associated-SABs (CA-SAB) occurring in children (≤20 yrs) in Denmark from 1990 to 2006. Controls were age-matched healthy individuals with no history of SAB. DNA obtained from cases and controls using the Danish Newborn Screening Biobank were genotyped for functional polymorphisms of DEFB1 by Sanger sequencing and copy number variation of the DEFB103 and DEFB4 genes using Pyrosequencing-based Paralogue Ratio Test (P-PRT). RESULTS: 193 ethnic Danish SAB cases with 382 age-matched controls were used for this study. S. aureus isolates represented a variety of bacterial (i.e., different spa types) types similar to SAB isolates in general. DEFB1 minor allele frequencies of rs11362 (cases vs. controls 0.47/0.44), rs1800972 (0.21/0.24), and rs1799946 (0.32/0.33) were not significantly different in cases compared with controls. Also, DEFB4/DEFB103 gene copy numbers (means 4.83/4.92) were not significantly different in cases compared with controls. CONCLUSIONS: Using a large, unique cohort of pediatric CA-SAB, we found no significant association between DEFB1 genetic variation or DEFB4/DEFB103 gene copy number and susceptibility for SAB.
Genetic Predisposition to Disease
Sequence Analysis, DNA
Published Version (Please cite this version)10.1371/journal.pone.0032315
Publication InfoAndersen, PS; Danish SAB Study Group Consortium; Feenstra, B; Fode, P; Fowler, Vance Garrison Jr; Jespersgaard, C; ... Stegger, M (2012). Genetic variability in beta-defensins is not associated with susceptibility to Staphylococcus aureus bacteremia. PLoS One, 7(2). pp. e32315. 10.1371/journal.pone.0032315. Retrieved from https://hdl.handle.net/10161/13320.
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Florence McAlister Professor of Medicine
Determinants of Outcome in Patients with Staphylococcus aureus Bacteremia Pathogenesis of Bacterial Infections Infections due to Resistant Gram Positive Organisms Tropical medicine/International Health