Impaired β-defensin Expression in Human Skin Links DEFB1 Promoter Polymorphisms With Persistent Staphylococcus Aureus Nasal Carriage

J Infect Dis. 2013 Feb 15;207(4):666-74. doi: 10.1093/infdis/jis735. Epub 2012 Nov 29.

Abstract

Background: Genetically determined variation in the expression of innate defense molecules may explain differences in the propensity to be colonized with Staphylococcus aureus.

Methods: We determined S. aureus nasal carriage in 603 volunteers; analyzed polymorphisms in the DEFB1 promoter at positions -52 G>A (rs1799946), -44 C>G (rs1800972), and -20 G>A (rs11362); and measured the content of human β-defensin 1 (hBD-1) and hBD-3 messenger RNA (mRNA) in 192 samples of healthy and experimentally wounded human skin.

Results: Compared with GGG at the positions -52/-44/-20, the ACG haplotype was more common among persistent S. aureus nasal carriers (odds ratio, 1.93; 95% confidence interval [CI], 1.2-3.1; P = .006) and was associated with reduced expression of hBD-1 (GGG>ACG>GCA; P < .001) and hBD-3 (GGG>GCA>ACG; P = .04) in skin when measured 72 hours after wounding. Furthermore, a 50% decrease in hBD-1 and hBD-3 mRNA expression in wounded skin increased the odds of persistent carriage by 1.45 (95% CI, .93-2.26; P = .1) and 1.48 (95% CI, 1.01-2.17; P = .04), respectively. Adjustment for known risk factors of persistent S. aureus carriage did not substantially change the associations of both DEFB1 haplotypes and β-defensin expression with S. aureus colonization.

Conclusions: DEFB1 polymorphisms may promote persistent S. aureus colonization by altering β-defensin expression in keratinocytes of human skin.

MeSH terms

  • Adult
  • Carrier State / immunology
  • Carrier State / microbiology*
  • Cross-Sectional Studies
  • Down-Regulation*
  • Female
  • Genetic Association Studies
  • Host-Pathogen Interactions
  • Humans
  • Keratinocytes / metabolism
  • Male
  • Nose / microbiology*
  • Polymorphism, Single Nucleotide / genetics*
  • Promoter Regions, Genetic / genetics*
  • Skin / cytology
  • Skin / immunology
  • Skin / metabolism
  • Staphylococcal Infections / microbiology
  • Staphylococcus aureus / isolation & purification*
  • Young Adult
  • beta-Defensins / genetics
  • beta-Defensins / metabolism*

Substances

  • DEFB1 protein, human
  • DEFB103A protein, human
  • beta-Defensins