Abstract
IntroductionHuman 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.MethodsCases 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).Results193 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.ConclusionsUsing 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.
Highlights
Human beta-defensins are key components of human innate immunity to a variety of pathogens, including Staphylococcus aureus
Using a murine S. aureus sepsis model, Ahn et al recently demonstrated that inbred A/J mice were highly susceptible to S. aureus infection as compared to C57BL6, and that this susceptibility was associated with regions on A/J chromosomes 8, 11, and 18, chromosomes that included defensin genes and several other innate immune genes [7]
S. aureus bacteremia (SAB) acquisition was classified as Hospital associated (HA)-SAB, Community associated (CA)-SAB or unknown, based on the time of positive SAB sampling after hospital admission
Summary
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. Investigators at Erasmus University recently suggested that variability within key innate immunity genes were associated with persistent S. aureus carriage [8]. Despite these findings, the precise genetic determinants for susceptibility to S. aureus infection in humans are unknown
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