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Genetic variability in beta-defensins is not associated with susceptibility to Staphylococcus aureus bacteremia.

Fode P, Larsen AR, Feenstra B, Jespersgaard C, Skov RL, Stegger M, Fowler VG, Danish SAB Study Group ConsortiumAndersen PS - PLoS ONE (2012)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department for Microbiological Surveillance and Research, Statens Serum Institut, Copenhagen, Denmark.

ABSTRACT

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.

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Related in: MedlinePlus

Power curves for an unpaired t-test with 193 cases and 382 controls, assuming equal variance in cases and controls and a significance level of 0.05.True difference in mean copy number is shown on the x-axis, and the power to detect such differences is shown on the y-axis. Curves are shown for three different copy number standard deviations: 1.1 (solid), 1.2 (dashed), and 1.3 (dotted).
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pone-0032315-g001: Power curves for an unpaired t-test with 193 cases and 382 controls, assuming equal variance in cases and controls and a significance level of 0.05.True difference in mean copy number is shown on the x-axis, and the power to detect such differences is shown on the y-axis. Curves are shown for three different copy number standard deviations: 1.1 (solid), 1.2 (dashed), and 1.3 (dotted).

Mentions: In the design phase of the study, we used published association results between higher copy number for β–defensin genes and risk of psoriasis [25] to estimate power for various sample sizes. The effect sizes seen in the study by Hollox et al [25] ranged from 0.25 to 0.4 in mean copy number difference between cases and controls, and the standard deviations of copy numbers in cases and controls ranged between 1.1 and 1.3. Using an unpaired t-test with an significance level of α = 0.05 and assuming equal variances in cases and controls, the power estimates based on these effect sizes ranged from 0.58 (true difference 0.25, standard deviation 1.3) to 0.98 (true difference 0.4, standard deviation 1.1) for 193 cases and 382 controls (see Figure 1 for power curves). Using the largest observed standard deviations in our study (1.17 in cases), the power was 0.67 for a true effect size of 0.25, and for an effect size of 0.40 the power was 0.97. Power calculations were performed using R.


Genetic variability in beta-defensins is not associated with susceptibility to Staphylococcus aureus bacteremia.

Fode P, Larsen AR, Feenstra B, Jespersgaard C, Skov RL, Stegger M, Fowler VG, Danish SAB Study Group ConsortiumAndersen PS - PLoS ONE (2012)

Power curves for an unpaired t-test with 193 cases and 382 controls, assuming equal variance in cases and controls and a significance level of 0.05.True difference in mean copy number is shown on the x-axis, and the power to detect such differences is shown on the y-axis. Curves are shown for three different copy number standard deviations: 1.1 (solid), 1.2 (dashed), and 1.3 (dotted).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3285211&req=5

pone-0032315-g001: Power curves for an unpaired t-test with 193 cases and 382 controls, assuming equal variance in cases and controls and a significance level of 0.05.True difference in mean copy number is shown on the x-axis, and the power to detect such differences is shown on the y-axis. Curves are shown for three different copy number standard deviations: 1.1 (solid), 1.2 (dashed), and 1.3 (dotted).
Mentions: In the design phase of the study, we used published association results between higher copy number for β–defensin genes and risk of psoriasis [25] to estimate power for various sample sizes. The effect sizes seen in the study by Hollox et al [25] ranged from 0.25 to 0.4 in mean copy number difference between cases and controls, and the standard deviations of copy numbers in cases and controls ranged between 1.1 and 1.3. Using an unpaired t-test with an significance level of α = 0.05 and assuming equal variances in cases and controls, the power estimates based on these effect sizes ranged from 0.58 (true difference 0.25, standard deviation 1.3) to 0.98 (true difference 0.4, standard deviation 1.1) for 193 cases and 382 controls (see Figure 1 for power curves). Using the largest observed standard deviations in our study (1.17 in cases), the power was 0.67 for a true effect size of 0.25, and for an effect size of 0.40 the power was 0.97. Power calculations were performed using R.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department for Microbiological Surveillance and Research, Statens Serum Institut, Copenhagen, Denmark.

ABSTRACT

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.

Show MeSH
Related in: MedlinePlus